phytoestrogens and Osteoporosis

Osteoporosis is a public health concern and a cause of bone loss, increased risk of skeletal fracture, and a heavy economic burden. It is common in postmenopausal women and the elderly and is impacted by dietary factors, lifestyle and some secondary factors. Although many drugs are available for the treatment of osteoporosis, these therapies are accompanied by subsequent side effects. Hence, dietary interventions are highly important to prevent osteoporosis. This review was aimed to provide a comprehensive understanding of the roles of dietary nutrients derived from natural foods and of common dietary patterns in the regulation of osteoporosis. Nutrients from daily diets, such as unsaturated fatty acids, proteins, minerals, peptides, phytoestrogens, and prebiotics, can regulate bone metabolism and reverse bone loss. Meanwhile, these nutrients generally existed in food groups and certain dietary patterns also play critical roles in skeletal health. Appropriate dietary interventions (nutrients and dietary patterns) could be primary and effective strategies to prevent and treat osteoporosis across the lifespan for the consumers and food enterprises.

Topics: Aged; Bone Density; Diet; Female; Fractures, Bone; Humans; Osteoporosis; Phytoestrogens

Functional foods have nutritional properties and organic functions, which are beneficial to health. Certain types of functional food components are so-called phytoestrogens, non-steroidal compounds derived from the metabolism of precursors contained in plants, which originate secondary metabotypes known to induce biological responses and by mimicry or modulating the action of endogenous estrogen. These molecules are involved in several physiological and pathological processes related to reproduction, bone remodeling, skin, cardiovascular, nervous, immune systems, and metabolism. This review aimed to present an overview of phytoestrogens regarding their chemical structure, actions, and effects in the organism given several pathologies. Several studies have demonstrated beneficial phytoestrogen actions, such as lipid profile improvement, cognitive function, menopause, oxidative stress, among others. Phytoestrogens effects are not completely elucidated, being necessary future research to understand the exact action mechanisms, whether they are via estrogen receptor or whether other hidden mechanisms produce these effects. Thus, this review makes a general approach to the phytoestrogen actions, beneficial effects, risk and limitations. However, the complexities of biological effects after ingestion of phytoestrogens and the differences in their metabolism and bioavailability indicate that interpretation of either risk or benefits needs to be made with caution.

Topics: Antioxidants; Cardiovascular Diseases; Cognition; Diet; Female; Humans; Isoflavones; Lipids; Menopause; Neuroprotective Agents; Osteoporosis; Oxidative Stress; Phytoestrogens; Plants; Receptors, Estrogen

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.

Topics: Animals; Bone and Bones; Bone Density; Botany; Female; Fractures, Bone; Herbal Medicine; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens

Selective estrogen receptor modulators (SERMs) are an increasingly important therapeutic modality that are used by clinicians on a daily basis. Unfortunately, clinicians have a limited understanding regarding the underlying mechanism(s) of how SERMs function and their increasingly useful role in the treatment of estrogen-responsive target tissues such as the breast, bone, vagina, uterine endometrium, and brain. This review will provide a basic understanding of our current knowledge of SERM pharmacodynamics and will highlight the clinical applications of Food and Drug Administration-approved SERMs in the treatment of vasomotor symptoms, osteoporosis, genitourinary syndrome of menopause, infertility, and breast cancer and its prevention. SERMs under development and natural phytoestrogens will also be reviewed.

Topics: Breast Neoplasms; Estrogens; Female; Humans; Osteoporosis; Phytoestrogens; Selective Estrogen Receptor Modulators

Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Topics: Abdominal Fat; Adult; Aged; Aged, 80 and over; Aging; Beer; Female; Humans; Middle Aged; Minerals; Organism Hydration Status; Osteoporosis; Phytoestrogens; Polyphenols; Postmenopause; Young Adult

Phytoestrogens are candidate drugs for the treatment of osteoporosis. Many experiments have been designed to investigate the preventive effects of phytoestrogens for osteoporosis; however, it is easy for a single dissenting result from animal experiments to mislead clinical investigations. Herein, we use meta-analysis to assess the evidence for a protective effect of phytoestrogens on ovariectomized rat models of osteopenia. With respect to osteoporosis, PubMed and Web of Science were searched from January 2000 to March 2013 for relevant studies of phytoestrogens in ovariectomized rats. Two reviewers independently selected and assessed the studies. Data were aggregated using a random effects model. Meta-analysis revealed that the phytoestrogen treatment group demonstrated a significantly higher femur bone mineral density and trabecular bone and lower bone turnover markers (serum alkaline phosphatase and serum osteocalcin) compared with the control ovariectomized group, thus showing a bone protective effect of phytoestrogens in ovariectomized rats. Subsequent sensitivity analyses indicated that the effect of phytoestrogens on serum alkaline phosphatase and serum osteocalcin are not robust. Despite the high heterogeneity in the systematic review of animal experiments, the present results indicated that phytoestrogens may offer the most potential for the prevention of bone loss by reducing the expected loss of trabecular bone and bone mineral density. Their effects are likely due to inhibition of bone resorption, but their benefits on bone formation are still unclear. Further studies are needed to assess the effect of phytoestrogens on bone formation and the efficacy and safety of individual phytoestrogens.

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Resorption; Databases, Factual; Female; Osteocalcin; Osteogenesis; Osteoporosis; Ovariectomy; Phytoestrogens; Rats

The chemical structure, classification, source, metabolism, physiological and health effects of plant phytoestrogens and mechanisms of their action are reviewed. The available knowledge suggests that phytoestrogens can affect a number of physiological and pathological processes related to reproduction, bone remodeling, skin, cardiovascular, nervous, immune systems and metabolism. Due to these effects, phytoestrogens and phytoestrogen-containing diet can be useful for the prevention and treatment of menopausal symptoms, skin aging, osteoporosis, cancer, cardiovascular, neurodegenerative, immune and metabolic diseases. Possible problems in understanding and application of phytoestrogens (multiple targets and multiple estrogen receptor -dependent and -independent mechanisms of action, the discrepancy between the results of experimental and clinical studies, adequate source of phytoestrogen) have been discussed.

Topics: Animals; Breast Neoplasms; Cardiovascular Diseases; Female; Humans; Osteoporosis; Phytoestrogens; Plant Preparations; Receptors, Estrogen; Treatment Outcome

Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.

Topics: Androgen Antagonists; Calcium, Dietary; Diabetes Mellitus, Type 2; Dietary Supplements; Fatty Acids; Humans; Male; Osteoporosis; Phytoestrogens; Prostatic Neoplasms; Selenium; Treatment Outcome; Vitamin D; Vitamin E

There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.

Topics: Antioxidants; Bone Density; Calcium; Diet; Dietary Supplements; Humans; Nutritional Requirements; Osteoporosis; Phytoestrogens; Vitamin D; Vitamins

Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to Thailand. It has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years. Indeed, it has been claimed that P. mirifica contains active phytoestrogens (plant substances with estrogen-like activity). Using high performance liquid chromatography, at least 17 phytoestrogens, mainly isoflavones, have been isolated. Thus, fairly considerable scientific researches, both in vitro in cell lines and in vivo in various species of animals including humans, have been conducted to date to address its estrogenic activity on the reproductive organs, bones, cardiovascular diseases and other climacteric related symptoms. The antioxidative capacity and antiproliferative effect on tumor cell lines have also been assessed. In general, P. mirifica could be applicable for preventing, or as a therapeutic for, the symptoms related to estrogen deficiency in menopausal women as well as in andropausal men. However, the optimal doses for each desirable effect and the balance to avoid undesired side effects need to be calculated before use.

Topics: Animals; Antioxidants; Chromatography, High Pressure Liquid; Climacteric; Humans; Molecular Structure; Neoplasms; Osteoporosis; Phytoestrogens; Phytotherapy; Pueraria

Phytoestrogens as selective estrogen receptor modulators like compounds may consider as a therapeutic option in osteoporosis. In this regard, the effect of phytoestrogens on bone biomarkers was examined in several trials which their results are controversial. We aimed this meta-analysis to evaluate the net effect of phytoestrogens on bone markers. A thorough search was conducted from 2000 to 2010 in English articles. All randomized clinical trials were reviewed, and finally, 11 eligible randomized clinical trials were selected for meta-analysis. Totally 1,252 postmenopausal women were enrolled in the study by considering the changes of pyridinoline (Pyd), desoxypyridinoline (Dpyd), bone alkaline phosphatase, and osteocalcin concentrations in urine and serum after phytoestrogens consumption. The urine Pyd and Dpyd levels decreased significantly in phytoestrogens consumers. Effect size and effect size for weighted mean difference of urine Pyd levels showed -1.229171 (95% confidence interval (CI) = -1.927639 to -0.530703) and -9.780623 (95% CI = -14.240401 to -5.320845), respectively, a significant results in comparison to control group and significant results for Dpyd -0.520132 (95% CI = -0.871988 to -0.168275) and -0.818582 (95% CI = -1.247758 to -0.389407), respectively. Meta-analysis indicates that phytoestrogens intake can prevent bone resorption, but its benefits on bone formation are not significant. This favorable effect was observed in low doses and in at least 3 weeks of phytoestrogens intake.

Topics: Biomarkers; Bone Resorption; Female; Humans; Osteogenesis; Osteoporosis; Phytoestrogens; Postmenopause; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Treatment Outcome

Many clinical studies have been carried out to determine the health benefits of soy protein and the isoflavones contained in soy. S-equol is not present in soybeans but is produced naturally in the gut of certain individuals, particularly Asians, by the bacterial biotransformation of daidzein, a soy isoflavone. In those intervention studies in which plasma S-equol levels were determined, a concentration of >5-10 ng/mL has been associated with a positive outcome for vasomotor symptoms, osteoporosis (as measured by an increase in bone mineral density), prostate cancer, and the cardiovascular risk biomarkers low-density lipoprotein cholesterol and C-reactive protein. These studies suggest that S-equol may provide therapeutic benefits for a number of medical needs.

Topics: Biomarkers; Biotransformation; C-Reactive Protein; Cardiovascular Diseases; Equol; Estrogen Receptor beta; Female; Humans; Intestines; Isoflavones; Lipoproteins, LDL; Male; Osteoporosis; Phytoestrogens; Prostatic Neoplasms; Risk Factors

Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well. Consequently, the question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. The answer is likely complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing. Phytoestrogens are present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy. Soy infant formula now constitutes up to a third of the US market, and soy protein is now added to many processed foods. As weak estrogen agonists/antagonists with molecular and cellular properties similar to synthetic endocrine disruptors such as Bisphenol A (BPA), the phytoestrogens provide a useful model to comprehensively investigate the biological impact of endocrine disruptors in general. This review weighs the evidence for and against the purported health benefits and adverse effects of phytoestrogens.

Topics: Animals; Brain; Breast Neoplasms; Diethylstilbestrol; Endocrine Disruptors; Female; Genitalia; Heart Diseases; Humans; Male; Menopause; Menstrual Cycle; Mice; Osteoporosis; Phytoestrogens; Puberty; Rats; Sexual Behavior; Soybean Proteins

Osteoporosis is characterized by reduced bone mass and structural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. Bone loss further increases in postmenopausal women when the ovaries stop making estrogens. Women undergoing treatment for osteoporosis require long-term dosing therapeutic regimens, that offer no symptomatic relief, and may cause side effects. To avoid this problem, many therapeutic alternatives have been proposed. Epidemiological data support a robust relationship between soy isoflavones, fracture incidence and bone mineral density in osteoporotic, postmenopausal women. These suggest that a high isoflavone intake, restores the metabolic balance of bone formation and resorption. However, this matter is still controversial and several reports show negative results, probably because different doses and/or isoflavones have been used. Although it is difficult to identify the specific isoflavone most involved in preventing or restoring bone loss, a review of current literature based on new encouraging preclinical and clinical data, indicates that aglycone genistein appears to be the most effective isoflavone in preserving bone health. Genistein aglycone, through a peculiar anti-osteoporotic dual mode of action, can positively regulate bone cell metabolism rebalancing bone turnover towards bone formation. Genistein in fact stimulates osteoblast and inhibits osteoclast function, mainly through the osteoprotegerin-sRANKL system. The positive results achieved by genistein aglycone intake, in terms of efficacy and safety, have stimulated the development of specially formulated medical food products for the clinical management of postmenopausal bone loss.

Topics: Animals; Bone and Bones; Clinical Trials as Topic; Genistein; Humans; Osteogenesis; Osteoporosis; Phytoestrogens; Protein Kinase Inhibitors

Nutrition is important in promoting bone health and in managing an individual with low bone mass or osteoporosis. In adult women and men, known losses of bone mass and microarchitecture occur, and nutrition can help minimize these losses. In every patient, a healthy diet with adequate protein, fruits, vegetables, calcium, and vitamin D is required to maintain bone health. Recent reports on nutritional remedies for osteoporosis have highlighted the importance of calcium in youth and continued importance in conjunction with vitamin D as the population ages. It is likely that a calcium intake of 1200 mg/d is ideal, and there are some concerns about excessive calcium intakes. However, vitamin D intake needs to be increased in most populations. The ability of soy products, particularly genistein aglycone, to provide skeletal benefit has been recently studied, including some data that support a new medical food marketed as Fosteum (Primus Pharmaceuticals, Scottsdale, AZ).

Topics: Adult; Bone and Bones; Bone Diseases, Metabolic; Calcium; Child; Food, Formulated; Fractures, Bone; Genistein; Humans; Nutrition Assessment; Nutritional Requirements; Nutritional Status; Osteoporosis; Phytoestrogens; Vitamin D; Vitamin D Deficiency

Interest in the physiologic and pharmacologic role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the classes of compounds known as the phytoestrogens, which embody several groups of non-steroidal estrogens, including isoflavones and lignans that are widely distributed within nature. The impact of dietary phytoestrogens on normal biologic processes was first recognized in sheep. Observations of sheep grazing on fields rich in clover and cheetahs fed high soy diets in zoos suggested that flavonoids and related phytochemicals can affect mammalian health. Endogenous estrogens have an important role not only in the hypothalamic-pituitary-gonadal axis, but also in various non-gonadal systems, such as cardiovascular systems, bone, and central nervous systems, and lipid metabolism. There have been several clinical studies of hormone replacement therapy (HRT) in post-menopausal women to examine whether HRT has beneficial effects on the cardiovascular system, bone fractures, lipid metabolism, and Alzheimer's disease. In addition, estrogen contributes to the development of some estrogen-dependent cancers, such as breast cancer and prostate cancer and the number of patients with these cancers is increasing in developed countries. Although recent mega-studies showed negative results for classical HRT in the prevention of some of these diseases, the molecules that interact with estrogen receptors are candidate drugs for various diseases, including hormone-dependent cancers. This review focuses on the molecular properties and pharmaceutical potential of phytoestrogens.

Topics: Alzheimer Disease; Animals; Breast Neoplasms; Cardiovascular Diseases; Dietary Supplements; Female; Glucose Metabolism Disorders; Hormone Replacement Therapy; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Postmenopause; Receptors, Estrogen; Sheep

Soybean isoflavones show structural similarity to estradiol and therefore are known as phytoestrogen. Recently, isoflavones have received a great deal of attention for their preventive roles against hormone dependent diseases including postmenopausal osteoporosis, hyperlipidemia and cancer. Particularly, a number of studies have reported that soybean isoflavones inhibited bone loss in both female and male osteoporotic animal models as well as in postmenopausal women. On the other hand, since a kind of tablet with concentrated isoflavones has been recently applied for foods for specified health use (FOSHU), which are functional foods permitted to label a health claim by the Ministry of Health, Labor and Welfare in Japan, Food Safety Commission submitted a report the upper limit of daily isoflavone aglycon intake from FOSHU as well as from soybean products. This report demonstrates the effects of isoflavones on bone metabolism and safety.

Topics: Animals; Bone and Bones; Female; Glycine max; Humans; Isoflavones; Male; Osteoporosis; Phytoestrogens; Postmenopause

Review on complementary and alternative therapies for climacteric symptoms.. Search for publications about complementary or alternative treatments for climacteric symptoms based on Cochrane Library and Medline (1966-2006) including the references from the identified clinical trials and reviews.. Cimicifuga may influence climacteric symptoms, especially hot flushes. Results for phytoestrogens, hop and Salvia seem promising but are less convincing. St. John's wort is an option for the treatment of moderate depressive symptoms. Phytoestrogens seem to have some potential for the prevention of osteoporosis and cardiovascular diseases. Results for the influence of lifestyle on hot flushes are conflicting, but interventions have demonstrated their use for the prevention of osteoporosis and cardiovascular diseases.. Lifestyle modifications, Cimicifuga and phytoestrogens may relieve climacteric symptoms. Phytoestrogens and Cimicifuga should not be given to breast cancer survivors.

Topics: Acupuncture; Adult; Aged; Aromatherapy; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Cimicifuga; Climacteric; Cohort Studies; Complementary Therapies; Contraindications; Depression; Diet; Dioscorea; Exercise; Female; Homeopathy; Hot Flashes; Humans; Humulus; Hydrotherapy; Hypericum; Life Style; Longitudinal Studies; MEDLINE; Middle Aged; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Extracts; Postmenopause; Prospective Studies; Randomized Controlled Trials as Topic; Relaxation Therapy; Salvia; Stress, Physiological; Surveys and Questionnaires; Survivors; Trifolium

With the increasing numbers of breast cancers survivors, menopause, its symptoms, and its physical complications are becoming more prevalent problems in this patient population. Hormonal replacement, which has been the cornerstone therapy of menopausal related symptoms for decades, recently has been shown to increase breast cancer incidence as well as risk of recurrence and no longer should be recommended. Menopausal symptoms and complications such as hot flashes, vaginal dryness, dyspareunia, and osteoporosis leading to fractures have a negative impact on the quality of life of both breast cancer survivors and the general postmenopausal population. The purpose of this review is to discuss the evidence for the use of alternative therapies for menopausal symptoms, thus providing guidance and recommendations that should facilitate therapeutic decisions in the daily practice of medical oncologists and primary care physicians.

Topics: Breast Neoplasms; Cardiovascular Diseases; Complementary Therapies; Estrogens; Female; Genitalia, Female; Hot Flashes; Humans; Menopause; Menopause, Premature; Osteoporosis; Phytoestrogens; Quality of Life; Survivors; Vasomotor System

Phytoestrogens are naturally occurring plant-derived phytochemicals, whose common biological roles are to protect plants from stress or to act as part of a plant's defense mechanism. Although composed of a wide group of nonsteroidal compounds of diverse structure, phytoestrogens have been shown to bind estrogen receptors and to behave as weak agonist/antagonist in both animals and humans. Phytoestrogens include mainly isoflavones (IF), coumestans, and lignans. These compounds are known to be present in fruits, vegetables, and whole grains commonly consumed by humans. IF are found in legumes--mainly soybeans--whereas flaxseed is a major source of lignans, and coumestans are significantly present in clover, alfalfa and soybean sprouts. 8-Prenyl flavonoids are common in vegetables. Bioavailability of IF requires an initial hydrolysis of the sugar moiety by intestinal beta-glucosidases to allow the following uptake by enterocytes and the flow through the peripheral circulation. Following absorption, IF are then reconjugated mainly to glucuronic acid and to a lesser degree to sulphuric acid. Gut metabolism seems key to the determination of the potency of action. Several epidemiological studies correlated high dose consumptions of soy IF with multiple beneficial effects on breast and prostate cancers, menopausal symptoms, osteoporosis, atherosclerosis and stroke, and neurodegeneration. For the relief of menopausal symptoms a consumption of 60 mg aglycones/day has been suggested; for cancer prevention a consumption between 50 and 110 mg aglycones/day is considered beneficial to reduce risks of breast, colon and prostate cancer; to decrease cardiovascular risk a minimum intake of 40-60 mg aglycones/day, together with about 25 g of soy protein has been suggested. For improvement in bone mineral density, 60-100 mg aglycones/day for a period of at least 6-12 months could be beneficial.

Topics: Biological Availability; Breast Neoplasms; Coronary Disease; Diet; Fruit; Glycine max; Health Promotion; Humans; Intestinal Absorption; Isoflavones; Osteoporosis; Phytoestrogens; Safety; Vegetables

Evidence of the effect of purified soy isoflavones and soy protein isolates containing isoflavones on bone health in rats and in humans is inconsistent. Differences may be because of synergies or antagonisms among the isoflavones, threshold or biphasic dose effects, life stage of animals or human subjects, estrogen status, and environment-genetic interactions, including the ability to produce metabolites upon ingestion of isoflavones. At this time, the benefits of soy protein and isoflavones on bone health are inconclusive. This overview will summarize these discrepancies and will suggest future studies to clarify the conditions under which these dietary substances can be helpful for bones.

Topics: Bone and Bones; Bone Development; Humans; Incidence; Isoflavones; Middle Aged; Osteoporosis; Phytoestrogens; United States

The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet.

Topics: Animals; Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Humans; Isoflavones; Models, Animal; Molecular Structure; Osteoporosis; Phytoestrogens; Receptors, Steroid; Selective Estrogen Receptor Modulators; Trifolium; Vitamin A

Research in animal models indicates that without estrogen, the effectiveness of exercise for increasing bone mineral in females is reduced. With decreased estrogen levels, there is an increase in the threshold at which strains are detected by bone, in turn reducing the transmission of mechanical to biochemical signals for bone formation. Studies combining estrogen replacement and exercise training in postmenopausal women have yielded mixed results but indicate that the combination of interventions may be more effective than either intervention alone for increasing bone mass. Given the continued debate over the risks and benefits of estrogen replacement, other compounds such as bisphosphonates or phytoestrogens may be preferred in combination with exercise training for optimally increasing bone mass and preventing osteoporotic fracture. Studies on animals show that the combination of bisphosphonate or phytoestrogen supplementation with exercise training is effective, but trials in humans are lacking.

Topics: Aged; Animals; Bone Density; Combined Modality Therapy; Diphosphonates; Estrogen Replacement Therapy; Exercise; Exercise Therapy; Female; Humans; Isoflavones; Middle Aged; Osteoporosis; Phytoestrogens; Plant Preparations

Topics: Adult; Aged; Estrogen Replacement Therapy; Female; Humans; Middle Aged; Osteoporosis; Pharmacists; Phytoestrogens

The aim of this article was to present a simple classification of phytoestrogens, their approximate content in food products as well as their synthesis, biotransformation and activity in human organism. Having various mechanisms of action, phytoestrogens display both beneficial and adverse effects on physiological processes. Several positive health effects have been associated with phytoestrogens, such as a protective role against the development of cancers, proestrogenic effects (particularly with postmenopausal women) and beneficial influence on cardiovascular and osseous systems. Adverse effects of phytoestrogens have been observed in fetuses and young specimens. Limited studies have displayed disorders in morphology and physiology of the male reproductive system. High plasma phytoestrogens level inhibits a cellular activity of some enzymes, e.g. enzymes involved in the synthesis of steroid hormones. Direct contact with exogenous, environmental estrogens depends on human diet and it can be variable in different populations.

Topics: Cardiovascular Diseases; Female; Fertility; Humans; Male; Neoplasms; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Preparations

Dietary supplements, especially those containing phytoestrogens, frequently are used to either promote health or prevent disease. An estimated 20 billion dollars was spent on dietary supplements in the year 2000. Approximately 40% to 55% of Americans use supplements on a regular basis and 24% of these supplements contain herbs. Phytoestrogens are defined as any compound that is structurally or functionally related to ovarian or placental estrogens and their active metabolites. These compounds are widely used for various disorders related to women's health.

Topics: Biomarkers; Bone and Bones; Bone Density; Clinical Trials as Topic; Dietary Supplements; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations

Topics: Acid-Base Equilibrium; Animals; Calcium, Dietary; Dietary Proteins; Estrogens, Non-Steroidal; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations; Vitamin D; Vitamin K

Osteoporosis has become a major public health problem. Because the biggest culprit in the process of bone loss is oestrogen deficiency, hormone replacement therapy remains the mainstay for prevention, but prophylaxis by this means is limited. Phyto-oestrogens deserve special mention because emerging data support the suggestion that these weakly oestrogenic compounds, present in plants, may prevent bone loss associated with the menopause and thus represent a potential alternative therapy for a range of hormone-dependent conditions, including postmenopausal symptoms. A substantial body of work in animal models in the past few years has provided convincing data for significant improvements in bone mass and other endpoints following feeding with soya. Thus, phyto-oestrogens appear to have potential promise for maintaining or modestly improving bone mass of human subjects when consumed at optimal dosages. However, we must appreciate the limits of the information reached before extrapolating to man and we need to gather more data before health professionals can actively advocate the increased consumption of soya. Indeed, it will be important further to characterise the physiological effects of phyto-oestrogens and their margins of safety.

Topics: Animals; Bone and Bones; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Guidelines as Topic; Isoflavones; Models, Animal; Osteoporosis; Phytoestrogens; Plant Preparations; Rats

Osteoporosis is a serious public health concern. Skeletal fragility, leading to spine and hip fractures, is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of life is critical for the formation and retention of a healthy skeleton. It is important to prevent bone loss from occurring, to identify potential risk factors, and to correct them. Many genetic and lifestyle factors influence the risk for osteoporosis. Among these, diet is believed to be one of the most important, especially the roles of calcium and vitamin D. Deficiency in other dietary factors--eg, protein, vitamin K, vitamin A, phytoestrogens, and other nutrients--might also contribute to the risk for osteoporosis. In this article, the roles of diet and nutritional supplementation in preventing and treating osteoporosis are reviewed.

Topics: Adolescent; Adult; Aged; Bone and Bones; Calcium, Dietary; Child; Child, Preschool; Diet; Dietary Supplements; Estrogens, Non-Steroidal; Female; Fractures, Bone; Humans; Infant; Infant, Newborn; Isoflavones; Life Style; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Quality of Life; Risk Factors; United States; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Phytoestrogens are a diverse group of plant-derived compounds that structurally or functionally mimic mammalian estrogens and show potential benefits for human health. The number of articles published on phytoestrogens has risen dramatically in the past couple decades. Further research continues to demonstrate the biological complexity of phytoestrogens, which belong to several different chemical classes and act through diverse mechanisms. This paper discusses the classification of phytoestrogens, methods of identification, their proposed mechanisms of action and botanical sources for phytoestrogens. The effects of phytoestrogens on breast and prostate cancers, cardiovascular disease, menopausal symptoms and osteoporosis will also be examined including research on benefits and risks.

Topics: Hot Flashes; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Preparations; Plants, Medicinal; Receptors, Estrogen; Research Design

Many women seek alternatives to hormone replacement therapy (HRT). Phytoestrogens are nonsteroidal compounds with estrogenic or antiestrogenic properties. Six of the 16 clinical trials suggest a significant reduction in alleviating symptoms but to a lesser degree than HRT. A meta-analysis showed that phytoestrogens improve lipid profile. The 14 recent clinical trials led, however, to divergent findings. Small clinical trials suggested a protective effect of phytoestrogens on bone metabolism. High concentration of phytoestrogens was associated with a reduction in breast cancer risk in case-control studies.

Topics: Aged; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Clinical Trials as Topic; Female; Hormone Replacement Therapy; Humans; Isoflavones; Lipids; Menopause; Middle Aged; Osteoporosis; Phytoestrogens; Plant Preparations; Risk Factors

Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.

Topics: Breast Neoplasms; Cardiovascular Diseases; Diet; Female; Glycine max; Humans; Hypolipidemic Agents; Isoflavones; Menopause; Osteoporosis; Phytoestrogens; Plant Preparations

The use of dietary phyto-oestrogens as a possible option for the prevention of osteoporosis has raised considerable interest because of the increased concern about the risks associated with the use of hormone-replacement therapy. However, the evidence in support of a bone-sparing effect in post-menopausal women is still not sufficiently convincing. Most studies have been performed on soyabean isoflavones (genistein and daidzein), either in the purified form or as a soyabean-based product or extract. In vitro studies using primary cell cultures or stabilised cell lines indicate that treatment with genistein may lead to a reduction in bone resorption, but effects on bone formation have also been shown. Investigations using animal models have provided convincing evidence of major improvements in bone mass or bone turnover following soyabean feeding. Cross-sectional observations in South-East Asian populations with moderately high intakes of soyabean isoflavones (50 mg/d) have shown that women in the high quartile of intake have higher bone mineral density (BMD) and reduced bone turnover, an effect that has not been shown in populations with low average intakes. Human trials have given an indication of a possible effect on lumbar spine BMD, although they have been either short term (<6 months) or methodologically weak. Unresolved issues are: the optimal dose compatible with safety; the individual differences in response that can be related to diet and genotypes; the duration of exposure. Furthermore, there needs to be an evaluation of the relative biological effects of phyto-oestrogens other than isoflavones (lignans, resorcylic acid lactones, flavanols, coumestans) that are also present in European diets.

Topics: Animals; Bone and Bones; Bone Density; Bone Development; Bone Resorption; Disease Models, Animal; Glycine max; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations

To revise and expand the 1996 Osteoporosis Society of Canada clinical practice guidelines for the management of osteoporosis, incorporating recent advances in diagnosis, prevention and management of osteoporosis, and to identify and assess the evidence supporting the recommendations.. All aspects of osteoporosis care and its fracture complications - including classification, diagnosis, management and methods for screening, as well as prevention and reducing fracture risk - were reviewed, revised as required and expressed as a set of recommendations.. Strategies for identifying and evaluating those at high risk; the use of bone mineral density and biochemical markers in diagnosis and assessing response to management; recommendations regarding nutrition and physical activity; and the selection of pharmacologic therapy for the prevention and management of osteoporosis in men and women and for osteoporosis resulting from glucocorticoid treatment.. All recommendations were developed using a justifiable and reproducible process involving an explicit method for the evaluation and citation of supporting evidence.. All recommendations were reviewed by members of the Scientific Advisory Council of the Osteoporosis Society of Canada, an expert steering committee and others, including family physicians, dietitians, therapists and representatives of various medical specialties involved in osteoporosis care (geriatric medicine, rheumatology, endocrinology, obstetrics and gynecology, nephrology, radiology) as well as methodologists from across Canada.. Earlier diagnosis and prevention of fractures should decrease the medical, social and economic burdens of this disease.. This document outlines detailed recommendations pertaining to all aspects of osteoporosis. Strategies for identifying those at increased risk (i.e., those with at least one major or 2 minor risk factors) and screening with central dual-energy x-ray absorptiometry at age 65 years are recommended. Bisphosphonates and raloxifene are first-line therapies in the prevention and treatment of postmenopausal osteoporosis. Estrogen and progestin/progesterone is a first-line therapy in the prevention and a second-line therapy in the treatment of postmenopausal osteoporosis. Nasal calcitonin is a second-line therapy in the treatment of postmenopausal osteoporosis. Although not yet approved for use in Canada, hPTH(1-34) is expected to be a first-line treatment for postmenopausal women with severe osteoporosis. Ipriflavone, vitamin K and fluoride are not recommended. Bisphosphonates are the first-line therapy for the prevention and treatment of osteoporosis in patients requiring prolonged glucocorticoid therapy and for men with osteoporosis. Nasal or parenteral calcitonin is a first-line treatment for pain associated with acute vertebral fractures. Impact-type exercise and age-appropriate calcium and vitamin D intake are recommended for the prevention of osteoporosis.. All recommendations were graded according to the strength of the evidence; where the evidence was insufficient and recommendations were based on consensus opinion alone, this is indicated. These guidelines are viewed as a work in progress and will be updated periodically in response to advances in this field.

Topics: Adult; Aged; Bone Density; Canada; Child; Diet; Diphosphonates; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Middle Aged; Osteoporosis; Phytoestrogens; Plant Preparations; Practice Guidelines as Topic; Prognosis; Randomized Controlled Trials as Topic; Risk Factors

Osteoporosis with increased risk of bone fracture is a disabling syndrome that naturally occurs as long as one ages and moves on two legs. Recent progress in bone cell biology has shed light on the mechanisms underlying the anti-osteoporotic properties of drugs that have been in use for a long time, providing a fresh stage for novel pharmacotherapies. In addition, large scale clinical trials developed in the past decade appear not only to rationalize the clinical utilities of these drugs but also to provide new concepts for the development of new therapeutic modalities. Progress in the fields of basic and clinical research field is briefly reviewed herein.

Topics: Alendronate; Androgens; Animals; Binding Sites; Bone Remodeling; Clinical Trials as Topic; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Evidence-Based Medicine; Humans; Isoflavones; Osteoblasts; Osteoclasts; Osteoporosis; Phytoestrogens; Plant Preparations; Selective Estrogen Receptor Modulators; Vitamin D; Vitamin K 2

Due to some severe side effects "classical" hormone replacement therapy (HRT) is currently being challenged by a therapy with phytoestrogens. Particularly soy and red clover derived isoflavones are advertised as selective estrogen receptor modulators (SERMs) with only desired and no undesired estrogenic effects. Evidence that this is the case however is scarce. Most studies investigating climacteric complaints did not find beneficial effects. A proposed beneficial effect on mammary cancer is unproven. The majority of studies however indicate an antiosteoporotic effect of isoflavones, while putative beneficial effects in the cardiovascular system are questionable due to the fact that estradiol which--like isoflavones--increase HDL and decrease LDL concentrations appear not to prevent arteriosclerosis in the human. In the urogenital tract, including the vagina, soy and red clover derived isoflavones are without effects. Cimicifuga racemosa extracts are traditionally used for the treatment of climacteric complaints. Evidence is now available that the yet unknown compounds in Cimicifuga racemosa extracts prevent climacteric complaints and may also have antiosteoporotic effects.

Topics: Bone and Bones; Breast Neoplasms; Cardiovascular System; Cimicifuga; Estrogens, Non-Steroidal; Female; Hormone Replacement Therapy; Humans; Isoflavones; Menopause; Osteoporosis; Phytoestrogens; Plant Extracts; Plant Preparations; Time Factors; Urogenital System

Despite the benefits of conventional hormone replacement therapy, some women are not candidates for this treatment and many others choose not to take it. As a result, there is growing interest among patients about natural alternatives. There is some evidence that phytoestrogens may offer protection against a wide range of human conditions, including breast cancer, cardiovascular disease, brain dysfunction, osteoporosis, and menopausal symptoms. The literature on the possible health benefits of phytoestrogens has expanded exponentially since the 1980s, mainly in response to funding initiatives by the U.S. government and soybean industries, and more lately by European and UK Ministries of Food. The physiological effects of phytoestrogens also have created a marketing opportunity that has been used by industry, particularly in soybean-producing countries such as the U.S. and Australia. Nevertheless, clinical applications for phytoestrogens are still in their infancy, and more interventional trials are required to reach definitive conclusions regarding their efficacy and safety, although they appear to represent a promising group of compounds, which may be useful in the future for the treatment of the menopausal syndrome. Also, the lack of clinical data presently available must signal caution in relation to the possible risk of adverse effects.. Obstetricians and Gynecologists, Family Physicians.. After completion of this article, the reader will be able to identify the various types of phytoestrogens, list the sources of phytoestrogens, and summarize the various effects of phytoestrogens.

Topics: Cardiovascular Diseases; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Neoplasms; Osteoporosis; Phytoestrogens; Plant Preparations; Postmenopause; Risk Factors

Phytoestrogens have been investigated at the epidemiological, clinical and molecular levels to determine their potential health benefits. The two major groups of phytoestrogens, isoflavones and lignans, are abundant in soy products and flax respectively, but are also present in a variety of other foods. It is thought that these estrogen-like compounds may protect against chronic diseases, such as hormone-dependent cancers, cardiovascular disease and osteoporosis. Furthermore, phytoestrogens are used as a natural alternative to hormone replacement therapy and to reduce menopausal symptoms. Phytoestrogens have been shown to induce both estrogenic and anti-estrogenic effects but their biological relevance and potency have not been well characterized. In children, consumption of soy-based formulas and soy milk can lead to high levels of exposure to phytoestrogens with only limited data available concerning potential benefits or adverse effects. Phytoestrogens are considered good candidates for use in natural therapies and as chemopreventive agents in adults. Safe and efficacious levels have yet to be established.

Topics: Biological Availability; Breast Neoplasms; Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Female; Food Analysis; Humans; Isoflavones; Lignans; Male; Menopause; Osteoporosis; Phytoestrogens; Plant Preparations; Plants; Prostatic Neoplasms

Topics: Bone Density; Breast Neoplasms; Cholesterol; Estrogens, Non-Steroidal; Female; Hormone Replacement Therapy; Hot Flashes; Humans; Isoflavones; Menopause; Osteoporosis; Phytoestrogens; Plant Preparations; Soybean Proteins

Topics: Animals; Bone Density; Breast Neoplasms; Cognition; Coronary Disease; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis; Patient Compliance; Phytoestrogens; Plant Preparations; Risk Assessment; Soybean Proteins; Treatment Outcome

The steroid hormone estrogen influences female and male reproductive system, 17-beta-oestradiol is the major human oestrogen. Phytoestrogens are naturally occurring oestrogens in many foods of plant origin. They are structurally and functionally similar to 17-beta-oestradiol or produce estrogenic effects. It is suggested that phytoestrogens could lower risk of diseases accompanied woman in meno- and postmenopausal stage. They are consider to decrease risk of breast, endometrial and ovarian cancer, osteoporosis, cardiovascular disease. This report presents the literature review on nutritious and health aspects connected with phytoestrogens. Generally authors confirm the possibility of beneficial health effects of phytoestrogens in humans.

Topics: Age Factors; Breast Neoplasms; Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Osteoporosis; Ovarian Neoplasms; Phytoestrogens; Plant Preparations; Plants, Edible; Time Factors; Uterine Neoplasms

Substantial evidence indicates that diets high in plant-based foods may explain the epidemiologic variance of many hormone-dependent diseases that are a major cause of mortality and morbidity in Western populations. There is now an increased awareness that plants contain many phytoprotectants. Lignans and isoflavones represent two of the main classes of phytoestrogens of current interest in clinical nutrition. Although ubiquitous in their occurrence in the plant kingdom, these bioactive nonnutrients are found in particularly high concentrations in flaxseeds and soybeans and have been found to have a wide range of hormonal and nonhormonal activities that serve to provide plausible mechanisms for the potential health benefits of diets rich in phytoestrogens. Data from animal and in vitro studies provide convincing evidence for the potential of phytoestrogens in influencing hormone-dependent states; although the clinical application of diets rich in these estrogen mimics is in its infancy, data from preliminary studies suggest beneficial effects of importance to health. This review focuses on the more recent studies pertinent to this field and includes, where appropriate, the landmark and historical literature that has led to the exponential increase in interest in phytoestrogens from a clinical nutrition perspective.

Topics: Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Health Promotion; Humans; Isoflavones; Male; Menopause; Nutritional Physiological Phenomena; Osteoporosis; Phytoestrogens; Plant Preparations; Plants, Edible; Structure-Activity Relationship

Topics: Breast Neoplasms; Cardiovascular Diseases; Clinical Trials as Topic; Estrogen Antagonists; Estrogens; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Osteoporosis; Phytoestrogens; Piperidines; Plant Preparations; Raloxifene Hydrochloride; Receptors, Estrogen; Survivors

This review will focus on antioestrogens and selective oestrogen receptor modulators (SERMS). The more traditional SERMS, clomiphene citrate and tamoxifen, will be reviewed along with such modern drugs as raloxifene and faslodex, with emphasis upon their actions on breast, uterus, bone and lipids. The future potential of these medications, in the management of oestrogen-dependent gynaecological conditions such as endometriosis, dysfunctional uterine bleeding, fibroids and breast cancer will be discussed.

Topics: Bone and Bones; Breast Neoplasms; Clomiphene; Estradiol; Estrogen Receptor Modulators; Estrogens, Non-Steroidal; Female; Fulvestrant; Genital Diseases, Female; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations; Plants; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Tamoxifen; Women's Health

Calcium and vitamin D can significantly impact bone mineral and fracture risk in women. Unfortunately, calcium intakes in women are low and many elderly have poor vitamin D status. Supplementation with calcium (approximately 1000 mg) can reduce bone loss in premenopausal and late postmenopausal women, especially at sites that have a high cortical bone composition. Vitamin D supplementation slows bone loss and reduces fracture rates in late postmenopausal women. While an excess of nutrients such as sodium and protein potentially affect bone mineral through increased calcium excretion, phytoestrogens in soy foods may attenuate bone loss through estrogenlike activity. Weight-bearing physical activity may reduce the risk of osteoporosis in women by augmenting bone mineral during the early adult years and reducing the loss of bone following menopause. High-load activities, such as resistance training, appear to provide the best stimulus for enhancing bone mineral; however, repetitive activities, such as walking, may have a positive impact on bone mineral when performed at higher intensities. Irrespective of changes in bone mineral, physical activities that improve muscular strength, endurance, and balance may reduce fracture risk by reducing the risk of falling. The combined effect of physical activity and calcium supplementation on bone mineral needs further investigation.

Topics: Accidental Falls; Adult; Aged; Bone and Bones; Bone Density; Calcium; Calcium, Dietary; Dietary Proteins; Estrogens, Non-Steroidal; Exercise; Female; Fractures, Bone; Humans; Isoflavones; Minerals; Muscle Contraction; Nutritional Physiological Phenomena; Osteoporosis; Osteoporosis, Postmenopausal; Physical Endurance; Phytoestrogens; Plant Preparations; Plants; Postural Balance; Risk Factors; Sodium, Dietary; Vitamin D; Walking; Weight Lifting; Weight-Bearing

Phytoestrogens are naturally occurring plant compounds which have oestrogenic and/or anti-oestrogenic activity. They are present in many human foodstuffs including beans, sprouts, cabbage, spinach, soyabean, grains and hops. The main classes are the isoflavones, coumestans and lignans. This review assesses the evidence that these substances may have adverse and/or beneficial impacts on the risk of several hormone-dependent diseases in humans. Evidence from studies of various animal species has demonstrated that ingestion of high levels of phytoestrogens can produce adverse effects on reproductive endpoints including fertility. Studies in laboratory animals have also shown that exposure to high doses of phytoestrogens during development can adversely affect brain differentiation and reproductive development in rodents, but may also have possible beneficial effects. In humans, there is a lack of information concerning the possible effects of high doses of phytoestrogens in infants and this should be addressed as a matter of priority so that any risks (or benefits) can be established. In adults, no current data exist to suggest that consumption of phytoestrogens at the levels normally encountered in the diet is likely to be harmful. Epidemiological studies suggest that foodstuffs containing phytoestrogens may have a beneficial role in protecting against a number of chronic diseases and conditions. For cancer of the prostate, colon, rectum, stomach and lung, the evidence is most consistent for a protective effect resulting from a high intake of grains, legumes, fruits and vegetables; it is not possible to identify particular food types or components that may be responsible. Dietary intervention studies indicate that in women soya and linseed may have beneficial effects on the risk of breast cancer and may help to alleviate postmenopausal symptoms. For osteoporosis, tentative evidence suggests phytoestrogens may have similar effects in maintaining bone density to those of the related pharmaceutical compound ipriflavone. Soya also appears to have beneficial effects on blood lipids which may help to reduce the risk of cardiovascular disease and atherosclerosis. Generally, however, little evidence exists to link these effects directly to phytoestrogens; many other components of soya and linseed are biologically active in various experimental systems and may be responsible for the observed effects in humans. It is concluded that dietary phytoestrogens may have a r

Topics: Adult; Animals; Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Fertility; Humans; Infant; Isoflavones; Male; Neoplasms; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Preparations; Plants

Practically all plant foods contain small amounts of the diverse phytoestrogen molecules that have the potential to improve health. Phytoestrogens, especially the soy-derived isoflavones, are receiving great scrutiny as food supplements for the purposes of both enhancing the health of tissues and preventing several common diseases, such as cardiovascular diseases, cancers of reproductive tissues and osteoporosis. Investigations of isoflavones, in particular, have recently become more prominent because of their oestrogenic activities. These actions may be as either partial oestrogen agonists or anti-oestrogens (inhibitors of natural oestrogen activity). For example, the isoflavones of soy, mainly genistein and daidzein, have been shown by at least three different laboratories to conserve bone in ovariectomized rodent models, and they probably have similar conservatory effects in higher mammalian species. Nevertheless, the only positive effects of phytoestrogens on bone observed so far in post-menopausal women have been small and limited to the lumbar vertebrae. Additional information on human studies currently in progress is needed before the efficacy of these preparations in human subjects is known.

Topics: Animals; Bone and Bones; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Osteoblasts; Osteoclasts; Osteoporosis; Phytoestrogens; Plant Preparations

Osteoporosis can be predicted to be a new burden to public health in Asia. Currently, the incidence of osteoporosis-related fractures is lower there than in most western communities. By the year 2050, however, 50% of the 6.3 million hip fractures which occur worldwide will be in Asians as a result of an aging population, a decrease in physical activity and westernization of lifestyles. The cost of treatment and cure of these patients will be enormous, a sufficient financial burden to consume current economic gain and cripple the future advancing development of Asian countries. Individual risk factors for osteoporosis have been identified by the extensive Mediterranean Osteoporosis Study (MEDOS). Fortunately, Asians, the rural population and farmers in particular, have the favorable lifestyle identified by the study, including high physical activity and exposure to sunlight. Strikingly, tea drinking, a daily habit in Asia, is also identified as a protective factor against osteoporosis. In addition, bioflavonoids and phytoestrogen-rich soybeans and vegetables are consumed in large quantities by Asians. A soy diet reduces mortality in breast and prostate cancer because it contains weak estrogens. The weakly estrogenic phytoestrogens require further study to demonstrate their pharmacological effect in reducing the rate of osteoporosis. Public health education, however, is needed to encourage the Asian population to maintain their traditionally good lifestyle and to reduce the risk factors for osteoporosis. In turn, these steps may reduce the public health burden by 2050.

Topics: Estrogens, Non-Steroidal; Fluorides; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations; Public Health; Risk Factors; Tea

This study systematically investigated the effects of phytoestrogen glabrene on postmenopausal osteoporosis in an ovariectomy (OVX) rat model. Glabrene administration (25, 50, and 100 mg/kg) for 13 weeks can significantly slow down the body weight gain and slightly increase the uterus weight of OVX rats. The increased levels of U-Ca, U-P levels, urine DPD/creatinine, serum ALP, OCN, triglycerides, and total cholesterol induced by OVX were dramatically inhibited in rats, whereas no difference occurred for S-Ca and S-P in all groups. Furthermore, glabrene can enhance bone mineral density of the right femur, fourth-lumbar vertebra and tibia and improve biomechanical parameters, such as femoral neck loading force, three-point bending of the tibia, and vertebral compression in OVX rats. Moreover, glabrene greatly suppressed the expression of TRAP protein but increased OPG and BGP protein expression in tibia tissue of OVX rats. In addition, OVX-induced reduction of Lrp-5, β-catenin, Runx2, and Osx protein expression was all restored by glabrene treatment. The present study indicated that glabrene might be a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis via activation of the Wnt/β-catenin signaling pathway.

Topics: Animals; beta Catenin; Body Weight; Dose-Response Relationship, Drug; Female; Isoflavones; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Up-Regulation; Uterus; Wnt Signaling Pathway

Trigonelline is a potent phytochemical present in fenugreek, which has strong anti-oxidant and phytoestrogenic activities. This study was carried out to investigate this estrogenic activity as a possible mechanisms involved in preventing the symptoms of osteoporosis in dexamethasone induced osteoporosis in rats.. Wistar rats were randomly divided into eight groups, six animals in each group. Osteoporosis was induced using dexamethasone 0.1mg/kg subcutaneously in rats for three times per week for 8 consecutive weeks and treatment with drugs up to 12 weeks as per the treatment schedule described. After 12 weeks, rats were sacrificed; blood samples were collected from each rat and the clear, non hemolysed supernatant sera was used for biochemical examinations. Femurs were used for Bone Mineral Density (BMD), microcomputed tomography (Micro CT), histology and biochemical examinations.. BMD, bone micro structure, serum calcium, phosphorus level and serum estradiol levels were decreased while serum PTH levels, SAP and acid phosphatase (ACP) were elevated in dexamethasone treated rats as compared to control (p<0.01). Dexmethasone treated animals showed loss of marrow at multifocal area, cartilage and trabeculae and thinning of trabeculae (bone resorption), zone of cartilage was poorly seen and fat cells in marrow. Trigonelline showed significant improvement and prevent the progression of osteoporosis by enhancing the BMD, restoring bone physiology.. Our results confirm the estrogenic activity of triogonelline, which is responsible for its effects; still, it needs further evaluation in other animal models to provide a more conclusive view for its therapeutic usefulness in osteoporosis.

Topics: Alkaloids; Animals; Bone Density; Dexamethasone; Disease Models, Animal; Femur; Humans; Osteoporosis; Phytoestrogens; Rats; Rats, Wistar; Trigonella; X-Ray Microtomography

Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Bone Regeneration; Core Binding Factor Alpha 1 Subunit; Estrogen Receptor alpha; Female; Genistein; Humans; Mice; Mice, Inbred ICR; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Phytoestrogens; Rats

Phytoestrogens are nonsteroidal plant compounds with similar chemical structures to mammalian estrogen capable of mimicking the effect of estrogen in selective tissues. A diet rich in phytoestrogens is associated with a variety of health benefits including decreased risks for heart disease, breast cancer, and osteoporosis. Obesity has long thought to be associated with improved bone density due to increased mechanical loading, but recent literature suggests obesity may actually decrease bone health. Daidzein, a soy-derived phytoestrogen, has been shown to improve parameters of bone health in lean animal models of osteoporosis but has not been tested in obese animals. Following a one-week acclimation to a standard AIN-93G diet, 19 five-week-old female obese Zucker rats (OZR) were randomly assigned to a modified AIN-93G diet containing either high daidzein (HD, 0.121 g kg-1 feed) or low daidzein (LD, 0.01 g kg-1 feed). After 8 weeks, tibias and femurs were removed to assess true density (Archimedes principal), mechanical strength (three-point bending test), and femoral osteogenic gene expression. Serum was collected to assess osteocalcin and deoxypyridinoline. Our results indicated that there were no significant differences between the measures for tibial or femoral true density or mechanical strength for the rats in the HD and LD diet groups. Similarly, there were no significant differences in gene expressions related to osteogenic pathways, or serum biomarkers of bone formation and resorption. Overall, an increased dose of daidzein from soy protein supplementation does not elicit an improvement in markers of bone health in obese Zucker rats.

Topics: Amino Acids; Animals; Biomarkers; Body Weight; Bone and Bones; Bone Density; Diet; Dietary Supplements; Disease Models, Animal; Energy Intake; Female; Femur; Gene Expression; Isoflavones; Obesity; Osteocalcin; Osteogenesis; Osteoporosis; Phytoestrogens; Rats; Rats, Zucker

Postmenopausal osteoporosis is a common disorder accompanied with estrogen deficiency in women. Plants containing phytoestrogens and amino acids have been used in the osteoporosis treatment. The present study aims to evaluate the estrogen-like activity of the Cicer arietinum extract (CAE) and its ability to inhibit osteoclastogenesis process. These achieved by investigating the binding of its active phytoestrogens (genistein, daidzein, formononetin and biochanin A) to the estrogen receptors (ER) α and β of rats and human in silico. In addition, in vivo study on ovariectomized (OVX) rats is performed. For in vivo study, twenty four rats were divided into four groups (n= 6). Group I is the sham control rats which administered distilled water. Groups II, III, and IV are OVX groups which administered distilled water, CAE (500 mg/kg), and alendronate; respectively. The docking study revealed that the phytoestrogens docked into the protein active site with binding energies comparable with that of estrogens (estriol and β-estradiol) which means the similarity between the estrogenic contents of CAE and the ensogenous ones. Additionally, in vivo study revealed that CAE reverse TRAP5b and RANKL levels that drastically increased in the untreated OVX group. But, it trigger upregulation of OPG, enhance the OPG/RANKL ratio and modulate the bone and uterus alterations of OVX group. Phytoestrogens and the bone-protective amino acids contents of CAE could be responsible for their estrogen-like effect and antiosteoporotic activity. These results concluded that CAE is an attractive candidate for developing a potential therapeutic cheap agent used as an alternative to the synthetic estrogen replacement therapy. Further, in vivo validation is required for its clinical application.

Topics: Alendronate; Animals; Bone Density Conservation Agents; Calcium-Binding Proteins; Cicer; Disease Models, Animal; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation; Genistein; Humans; Isoflavones; Membrane Glycoproteins; Molecular Docking Simulation; Osteogenesis; Osteoporosis; Osteoprotegerin; Ovariectomy; Phytoestrogens; Phytotherapy; Protein Structure, Secondary; RANK Ligand; Rats; Receptors, Cytoplasmic and Nuclear; Receptors, Peptide

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg

Topics: Animals; Cancellous Bone; Drug Evaluation, Preclinical; Genistein; Male; Osteoporosis; Phytoestrogens; Phytotherapy; Rats; Rats, Wistar; Thyroid Epithelial Cells

We investigate the consequence of adjuvant anastrozole (ANA) in monotherapy or associated with biochanin A (BCA) in ovariectomized (OVX) rat model and the degree of developing bone loss in both conditions.. Sixty female rats were assigned to six groups. Five groups were bilaterally OVX, and one was sham operated. The five groups were; ANA group (0.5 mg/kg b.wt orally), BCA (5 mg/kg b.wt intraperitoneally (I/P), co-treated group (BCA + ANA), two control groups receiving even distilled water orally or DMSO I/P for twenty weeks. Bone turnover biomarkers BALP, OC, PTH, TRAP and TNFα were determined in serum. Bone mineral content, histological and morphometric measurements on rat femurs were performed. BMD by X-ray technique on tibias of rats and CT analysis of lumbar vertebrae of all treated and sham groups were applied.. There was marked elevation in bone turnover biomarkers with high serum Ca and P content in the ANA-treated rats. Moreover marked elevation of TNFα, PTH, TC and TG, ANA caused severe changes in the BMD detected by X-ray in tibial bones and CT analysis of lumbar vertebrae of OVX rats. While I/P injection of BCA ameliorated the adverse bone health decrements caused by ANA.. The study highlights the importance of the BCA supplementation in accordance with the ANA therapy in case of ovariectomized rat model of osteoporosis which is clinically presented in Postmenopausal women with breast cancer during which considerable risk of developing osteoporosis is predicted during treatment.

Topics: Adjuvants, Pharmaceutic; Anastrozole; Animals; Female; Genistein; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley

While current therapies for osteoporosis focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs).. To investigate the effects of glyceollins, structural derivatives of daidzein, on osteogenesis of ASCs and BMSCs.. Herein, the osteoinductive effects of glyceollin I and glyceollin II were assessed and compared to estradiol in ASCs and BMSCs. The mechanism by which glyceollin II induces osteogenesis was further examined.. The ability of glyceollins to promote osteogenesis of ASCs and BMSCs was evaluated in adherent and scaffold cultures. Relative deposition of calcium was analyzed using Alizarin Red staining, Bichinchoninic acid Protein Assay, and Alamar Blue Assay. To further explore the mechanism by which glyceollin II exerts its osteoinductive effects, docking studies of glyceollin II, RNA isolation, cDNA synthesis, and quantitative RT-PCR (qPCR) were performed.. In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, or glyceollin II demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol and glyceollin I. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation.. The ability of glyceollin II to induce osteogenic differentiation in ASCs and BMSCs indicates that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis.

Topics: Adipose Tissue; Adult; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Estradiol; Female; Glycine max; Humans; Mesenchymal Stem Cells; Middle Aged; Osteogenesis; Osteoporosis; Phytoestrogens; Pterocarpans; Stem Cells; United States

EXECUTIVE SUMMARY This American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) Position Statement is designed to update the previous menopause clinical practice guidelines published in 2011 but does not replace them. The current document reviews new clinical trials published since then as well as new information regarding possible risks and benefits of therapies available for the treatment of menopausal symptoms. AACE reinforces the recommendations made in its previous guidelines and provides additional recommendations on the basis of new data. A summary regarding this position statement is listed below: New information available from randomized clinical trials and epidemiologic studies reported after 2011 was critically reviewed. No previous recommendations from the 2011 menopause clinical practice guidelines have been reversed or changed. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, selective estrogen-receptor modulators (SERMs), and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, SERMs, and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. New recommendations in this position statement include: 1.. the use of menopausal hormone therapy in symptomatic postmenopausal women should be based on consideration of all risk factors for cardiovascular disease, age, and time from menopause. 2.. the use of transdermal as compared with oral estrogen preparations may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease. 3.. when the use of progesterone is necessary, micronized progesterone is considered the safer alternative. 4.. in symptomatic menopausal women who are at significant risk from the use of hormone replacement therapy, the use of selective serotonin re-uptake inhibitors and possibly other nonhormonal agents may offer significant symptom relief. 5.. AACE does not recommend use of bioidentical hormone therapy. 6.. AACE fully supports the recommendations of the Comité de l'Évolution des Pratiques en Oncologie regarding the management of menopause in women with breast cancer. 7.. HRT is not recommended for the prevention of diabetes. 8.. In women with previously diagnosed diabetes, the use of HRT should be individualized, taking in to account age, metabolic, and cardiovascular risk factors.. AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CAC = coronary artery calcification; CEE = conjugated equine estrogen; CEPO = Comité de l'Évolution des Pratiques en Oncologie; CAD = coronary artery disease; CIMT = carotid intima media thickness; CVD = cardiovascular disease; FDA = Food and Drug Administration; HDL = high-density lipoprotein; HRT = hormone replacement therapy; HT = hypertension; KEEPS = Kronos Early Estrogen Prevention Study; LDL = low-density lipoprotein; MBS = metabolic syndrome; MPA = medroxyprogesterone acetate; RR = relative risk; SERM = selective estrogen-receptor modulator; SSRI = selective serotonin re-uptake inhibitor; VTE = venous thrombo-embolism; WHI = Women's Health Initiative.

Topics: Administration, Cutaneous; Administration, Oral; Aged; Amines; Breast Neoplasms; Cardiovascular Diseases; Cimicifuga; Cognition; Cyclohexanecarboxylic Acids; Diabetes Mellitus; Endocrinology; Estradiol; Estrogen Replacement Therapy; Estrogens; Excitatory Amino Acid Antagonists; Female; Gabapentin; gamma-Aminobutyric Acid; Hot Flashes; Humans; Menopause; Middle Aged; Osteoporosis; Phytoestrogens; Phytotherapy; Progesterone; Progestins; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Societies, Medical; Thrombosis; Vasomotor System

A novel soy protein aggregate enriched with isoflavones (SPA-IS), a mixture of soy protein and isoflavones (Mix), isoflavones (IS), and the soy protein were obtained to investigate the preventive effects on osteoporosis induced by retinoic acid in Kunming mice.. The serum osteocalcin levels in the Mix and SPA-IS groups decreased compared with the model group (mice showing retinoic acid-induced osteoporosis) (P < 0.05). The trabecular analysis results showed an increased preventive effect of the SPA-IS group over the Mix group, the IS group, and the soy protein group. The results of both left tibial maximum load and the 4th lumbar structural strength differ between the IS and the SPA-IS groups.. The SPA-IS exhibited obvious oestrogenic activities on retinoic acid-induced osteoporosis in Kunming mice compared to Mix, IS, and soy protein. The results suggest that there is a potential use for SPA-IS in the treatment of osteoporosis induced by intake of retinoic acid. The improvement of bone indicators might be attributed to the formation of aggregate particles and the improvement of IS solubility.

Topics: Animals; Bone and Bones; Bone Density; Female; Glycine max; Isoflavones; Mice; Osteocalcin; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Extracts; Solubility; Soybean Proteins; Tretinoin

Although it has been clearly shown that Pueraria mirifica and its phytoestrogens can mimic estrogen in preventing bone loss, as osteoporosis is an asymptomatic disease, the therapeutic effects of P. mirifica should be acknowledged. In this study, 6-month-old female rats were ovariectomized, kept for 4 weeks to induce bone loss, divided into five groups, and treated with P. mirifica at doses of 0, 5, 25, and 50 mg/kg BW/day (PM0, PM5, PM25, and PM50 groups, respectively) or 7 mg/kg BW/day of puerarin (PU group) for 12 weeks. Only the trabecular bone mineral densities (BMDs) of tibia metaphysis (at the 12th, 14th, and 16th week) and total and trabecular BMDs of L4 (at the 16th week) of the PM50 group were significantly higher than those of the PM0 group. However, the BMDs of tibia metaphysis and L4 at the 16th week of the study period were kept significantly lower than those of the 0 week, and the BMD was also significantly lower than that of the 4th week for tibia metaphysis. The trabecular bone area (BV/TV), trabecular number (Tb.N), and osteoblast surface (Ob.S/BS) were significantly higher, and trabecular space (Tb.Sp) was significantly lower in the PM50 group, as compared with those of the PM0 group. This study indicates that P. mirifica could be used as an anti-osteoporotic agent for postmenopausal women. Since P. mirifica could mainly retain bone mass at the levels before bone loss is initiated, the use of other anabolic agents in combination with P. mirifica is recommended for osteoporotic patients.

Topics: Animals; Bone Density; Bone Density Conservation Agents; Estrogens; Female; Humans; Isoflavones; Osteoblasts; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Extracts; Pueraria; Rats; Rats, Sprague-Dawley; Tibia

This study evaluates the effect of isoflavone cladrin on high-fat diet (HFD)-induced bone loss and adipogenesis.. Thirty-two 4-week-old male C57BL/6J mice were divided into four groups: a standard diet group, a HFD group and HFD group with cladrin (5 and 10 mg/kg per day orally) for 12 weeks. The effect of cladrin on bone micro-architecture, bone marrow cell lineages and hyperlipidaemia were assessed. For assessing anti-adipogenic activity of cladrin, 3T3-L1 cells were used.. Cladrin attenuated HFD-induced hyperlipidaemia and bone loss by preserving bone micro-architecture and strength. Effect of cladrin was found at the level of bone marrow progenitor cells. Gene expression profile of cladrin-treated mice bone showed upregulation of osteoblast and downregulation of adipogenic transcription factors and increased OPG/RANKL ratio. Cladrin inhibited cellular lipid accumulation through downregulation of transcription factors such as PPAR-γ and C/EBP-α and modulated the expression of major adipokines involved behind obesity stimulation without eliciting cell cytotoxicity in 3T3-L1 adipocytes.. We conclude that cladrin may improve obesity-induced bone loss and hyperlipidaemia in mice fed HFD and adipogenesis in 3T3-L1 cells by modifying adipokines and could offer clinical benefits as a supplement to treat obesity-induced disorders.

Topics: 3T3-L1 Cells; Adipogenesis; Adipokines; Adipose Tissue; Animals; Bone and Bones; Butea; Diet, High-Fat; Isoflavones; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Osteoporosis; Osteoprotegerin; Phytoestrogens; Phytotherapy; Plant Extracts; RANK Ligand; Transcription Factors

Daidzein is an isoflavone derived from soybeans that exerts preventive effects on bone loss in ovariectomized (OVX) animals. These effects have been correlated with increasing serum equol levels. In the present study, we investigated the effects of antibiotic intake on equol metabolism from daidzein, and the corresponding levels of bone loss in OVX mice.. Eight-week-old female ddY mice (n = 42) were either ovariectomized (OVX) or subjected to a sham operation (sham). OVX mice were then divided into six dietary subgroups: control diet (control), 0.3 % kanamycin diet (KN), 0.1 % daidzein diet (Dz), 0.1 % daidzein and 0.0375 % kanamycin diet (Dz+KN3.75), 0.1 % daidzein and 0.075 % kanamycin diet (Dz+KN7.5), and 0.1 % daidzein and 0.3 % kanamycin diet (Dz+KN30). The mice were fed their respective diets for 4 weeks.. Uterine weight and femoral bone mineral density (BMD) were significantly lower in the OVX mice compared in the sham mice. No significant differences in uterine weight were observed among all OVX dietary subgroups. The Dz subgroup was found to exhibit higher plasma equol and O-desmethylangolensin (O-DMA) concentrations, as well as greater femoral BMD, compared to all other OVX subgroups. Furthermore, when compared to the Dz group, kanamycin intake decreased plasma equol and O-DMA concentrations, as well as femoral BMD in the OVX mice.. These results suggest that kanamycin intake inhibited the conversion of daidzein to equol and O-DMA, blocking the preventive effects of daidzein on bone loss in OVX mice. Therefore, the bone-protective effects of daidzein intake may be predominantly associated with increased plasma concentrations of either equol or O-DMA.

Topics: Administration, Oral; Animals; Biotransformation; Body Weight; Bone Density; Diet; Disease Models, Animal; Equol; Female; Femur; Humans; Isoflavones; Kanamycin; Mice; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Uterus

Puerarin is a phytoestrogen that shows osteogenic effects. Meanwhile, zinc stimulates bone formation and inhibits bone resorption. The study aims to investigate the effects of coadministration of puerarin (low dose) and zinc on bone formation in ovariectomized rats.. Co-administration or use alone of puerarin (low dose) and/or zinc were gavaged in OVX rats. The estrogen-like effects were detected by the uterus weight, the histologic observation and the IGF-1 protein expression. The osteogenic effects were determined by bone histomorphometric and mechanical parameters, osteogenic and adipogenic blood markers, and so on.. The results showed that oral administration of puerarin (low dose) plus zinc didn't significantly increase uterus weight. The glandular epithelial of endometrium had no proliferation and no protein expression of IGF-1. Moreover, co-administration attenuated bone loss and biomechanical decrease more than single use of puerarin or zinc (p<0.05). Next, combined administration of puerarin and zinc promoted the serological level of osteocalcin, bone marrow stromal cell (BMSC) proliferation, and the expression of alkaline phosphatase (ALP), and suppressed the serological level of adiponectin and adiposity in bone marrow (BM).. In conclusion, co-administrated puerarin (low dose) and zinc can partially reverse OVX-induced bone loss and suppress the adiposity of BM in rats, which shed light on the potential use of puerarin and zinc in the treatment of osteoporosis.

Topics: Adipogenesis; Adiponectin; Adiposity; Animals; Biomechanical Phenomena; Bone Marrow; Cells, Cultured; Female; Insulin-Like Growth Factor I; Isoflavones; Osteocalcin; Osteoporosis; Ovariectomy; Phytoestrogens; Rats, Sprague-Dawley; Tibia; Zinc

Topics: Absorptiometry, Photon; Ascorbic Acid; Bone Density Conservation Agents; Calcium, Dietary; Denosumab; Female; Humans; Life Style; Magnesium; Male; Osteoporosis; Phosphorus; Phytoestrogens; Risk Factors; Teriparatide; Vitamin A; Vitamin D; Vitamin K

New Zealand is a rich source of food components that may have bioactivity on bone. Docosahexaenoic acid (DHA) from fish oil has been shown to maintain bone in ovariectomised (OVX) rats. Kiwifruit, a source of fibre and carotenoids, may also affect bone via a prebiotic as well as direct cell-based mechanisms. We aimed to 1) ascertain the effects of DHA on two cell models, including interactions with soy isoflavones; 2) and investigate the specific effects of carotenoids from kiwifruit as well as whole kiwifruit in cell-based and rodent models as well as in a human study. RAW 264.7 mouse monocytes or mouse bone marrow was used to generate osteoclasts (OC). Cells were exposed to the agents between 5 and 21 d and formation and activity of OC measured, including molecular markers. DHA inhibited OC formation in both cell models, including expression of cathepsin K, NFATc1 as well as actin ring formation. Combination with isoflavones enhanced these effects. In OVX rats and mice fed with kiwifruit for 8 wk, green kiwifruit reduced the rate of bone loss after OVX, and in mice it reduced C-telopeptide of Type 1 collagen (CTX) levels and RANKL expression while in menopausal women, green kiwifruit affected blood lipids and bone markers positively.

Topics: Actinidia; Animals; Bone and Bones; Bone Density; Bone Resorption; Carotenoids; Diet; Docosahexaenoic Acids; Female; Fruit; Functional Food; Glycine max; Humans; Isoflavones; Mice; New Zealand; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; RAW 264.7 Cells

Millettia macrophylla Benth is a Cameroonian medicinal plant traditionally used to alleviate menopause-related problems. The methanol soluble fraction of this plant was shown to exhibit estrogenic effects in vitro in Human Embryonic kidney cells, and in vivo on ovariectomized rat following the classical uterotrophic assay. Since estrogens have been involved in bone remodeling process, the present study then aimed at evaluating bone loss preventive effects of the methanol soluble fraction of Millettia macrophylla (MM-met) in ovariectomized rat model.. Twenty-five healthy Wistar female rats (3-month-old) were randomly assigned to a sham-operated group and to four treated ovariectomized (OVX) groups. Treatments lasted 8 weeks and animals were sacrificed. The uterus, the femoral and the tibia bones of each animal were collected, weighed and fixed in 10% formalin for histological analysis.. Results showed that ovariectomy decreased uterine wet weight (p<0.01), induced body weight gain (p<0.01), decreased both femoral and tibia bone density and mineral content and increased alkaline phosphatase activity (p<0.05). E2V and MM-met treatments in general prevented bone mass loss and/or bone density loss. At all tested doses, MM-met induced a significant decrease of alkaline phosphatase activity (p<0.05). As observed with E2V, MM-met also induced a significant protective effect on bone, and this was indicated by an abundance of bone marrow in an almost intact trabecular network.. The overall results show that the methanol soluble fraction of Millettia macrophylla may prevent ovariectomy-induced bone mass loss and deterioration of the trabecular microarchitecture.

Topics: Alkaline Phosphatase; Animals; Body Weight; Bone Density; Bone Density Conservation Agents; Bone Marrow; Disease Models, Animal; Female; Femur; Leg Bones; Millettia; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats, Wistar; Tibia

Icariin, Genistein, and Hispidulin have been proven to have estrogen-like and antiosteoporotic activity and can be potentially used for the treatment of osteoporosis. The present study found that Icariin, Genistein, and Hispidulin treatments, emulating estrogen, significantly contributed to bone density. Comparative effects of Icariin, Genistein, and Hispidulin with estrogen on in ovariectomized rats were investigated. Our results showed that genistein was found to have superior bone protective effects against osteoporosis among genistein, Icariin, and Hispidulin.

Topics: Animals; Biomarkers; Blood Chemical Analysis; Body Weight; Bone and Bones; Bone Density; Female; Flavones; Flavonoids; Genistein; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Urinalysis; Uterus

Postmenopausal osteoporosis affects millions of women, being estrogen deficiency the key factor in the pathogenesis of involutional osteoporosis. Fracture prevention is one of the public health priorities worldwide. Different treatments for osteoporosis are available. The various options are aimed to maintain bone health and decrease the risk of fractures. The majority of these drugs are antiresorptive agents, i.e., drugs that lower bone turnover, inhibiting osteoclastic bone resorption. Dietary sources of calcium intake and vitamin D are ideal, while pharmachological supplements should be used if diet alone cannot provide the recommended daily intake. Bisphosphonates are first-line therapy for patients with established osteoporosis at high risk of fracture. Some serious, but rare, adverse events have been associated with their long-term administration. The monoclonal antibody to RANKL, named denosumab, administered as a 60-mg subcutaneous injection every 6 months, is a valuable option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, who are unable to take other osteoporosis treatments. Teriparatide (PTH 1-34) is the only available osteoanabolic drugs for osteoporosis treatment at present. Its use is limited to severe osteoporosis because of the high cost of the treatment. In climacteric women, in different stages of menopausal transition, and beyond, hormone replacement therapy at different doses (HRT) rapidly normalizes turnover, preventing and/or treating osteoporosis. HRT is able to preserve and even increase BMD at all skeletal sites, leading to a significant reduction in vertebral and non-vertebral fractures. Selective estrogen modulators (SERMs) as raloxifene and bazedoxifene reduce bone turnover and maintains or increases vertebral and femoral BMDs in comparison to placebo and reduces the risk of vertebral and new vertebral fractures, in high risk women. The combination of a SERM with an estrogen has been defined as tissue selective estrogen complex (TSEC). The bazedoxifene with conjugated estrogen is able to reduce climacteric symptoms, reducing bone turnover and preserving BMD. Studies investigating the actions of phytoestrogens on BMD or bone turnover are largely contradictory, making them inconclusive. At the present time, phytoestrogens cannot be recommended for postmenopausal osteoporosis. In conclusion, the use of HRT for osteoporosis prevention is based on biology, epidemiology, animal and p

Topics: Anabolic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Female; Hormone Replacement Therapy; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Phytoestrogens; Radiography; Risk Factors; Selective Estrogen Receptor Modulators; Teriparatide; Thiophenes; Treatment Outcome

Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein and daidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal stem cells (BMSCs). Herein, the effects of daidzein analogs on the osteogenic differentiation efficiency of human BMSC and adipose-derived stromal/stem cells (ASC) were explored.. BMSCs and ASCs underwent osteogenic differentiation in the presence of vehicle, 17β-estradiol (E2), phytoestrogens, or daidzein analogs. Cells were stained for alkaline phosphatase (ALP) enzymatic activity, calcium deposition by alizarin red s, and phosphate mineralization by silver nitrate. Gene expression analysis was conducted on cells treated with daidzein analogs.. Cells treated with E2, daidzein, or genistein increased calcium deposition by 1.6-, 1.5-, and 1.4-fold, respectively, relative to vehicle-treated BMSCs and 1.6-, 1.7-, and 1.4-fold relative to vehicle-treated ASCs, respectively. BMSCs treated with daidzein analog 2c, 2g, and 2l demonstrated a 1.6-, 1.6-, and 1.9-fold increase in calcium deposition relative to vehicle-treated BMSCs, respectively, while ASCs treated with daidzein analog 2c, 2g, or 2l demonstrated a 1.7-, 2.0-, and 2.2-fold increase in calcium deposition relative to vehicle-treated ASCs, respectively. Additional analysis with BMSCs and ASCs was conducted in the more efficient compounds: 2g and 2l. ALP activity and phosphate mineralization was increased in 2g- and 2l-treated cells. The analysis of lineage specific gene expression demonstrated increased expression of key osteogenic genes (RUNX2, c-FOS, SPARC, DLX5, SPP1, COL1A1, IGF1, SOST, and DMP1) and earlier induction of these lineage specific genes, following treatment with 2g or 2l, relative to vehicle-treated cells. Estrogen receptor (ER) inhibitor studies demonstrated that ER antagonist fulvestrant inhibited the osteogenic differentiation of 2g in BMSCs and ASCs, while fulvestrant only attenuated the effects of 2l, suggesting that 2l acts by both ER dependent and independent pathways.. These studies provide support for exploring the therapeutic efficacy of daidzein derivatives for the treatment of osteoporosis. Furthermore, the patterns of gene induction differed following treatment with each daidzein analog, suggesting that these daidzein analogs activate distinct ER and non-ER pathways to induce differentiation in BMSCs and ASCs.

Topics: Adult Stem Cells; Alkaline Phosphatase; Bone Density Conservation Agents; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Drug Evaluation, Preclinical; Estradiol; Female; Fulvestrant; Humans; Inhibitory Concentration 50; Isoflavones; Mesenchymal Stem Cells; Osteogenesis; Osteoporosis; Phytoestrogens; Receptors, Estrogen

Isoflavones are naturally occurring plant chemicals belonging to the "phytoestrogen" class. The aim of the present study was to examine the effects of isoflavones obtained from Cordyceps sinensis (CSIF) on development of estrogen deficiency-induced osteoporosis in ovariectomized rats.. After the rats were treated orally with CSIF, serum alkaline phosphatase (ALP), tartarate resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine (HCY), C-terminal crosslinked telopeptides of collagen type I (CTX), estradiol and interferonγ (IFN-γ) level were examined. At the same time, the urine calcium, plasma calcium, plasma phosphorus and the mass of uterus, thymus and body were also examined.. The beneficial effects of CSIF on improvement of osteoporosis in rats were attributable mainly to decrease ALP activity, TRAP activity, CTX level and IFN-γ level. At the same time, CSIF also increase the OC and estradiol level in ovariectomized osteopenic rats. The histological examination clearly showed that dietary CSIF can prevent bone loss caused by estrogen deficiency.. The significant estrogenic activity of CSIF demonstrated that CSIF has significant estrogenic effects in OVX rats.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biological Products; Bone Density Conservation Agents; Bone Diseases, Metabolic; Collagen Type I; Cordyceps; Estradiol; Estrogens; Female; Humans; Interferon-gamma; Isoflavones; Osteocalcin; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Rats; Rats, Wistar; Uterus

Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems, has been reported to enhance bone regeneration in MC3T3-E1 cells in vitro. The objectives of this study were to investigate the antiosteoporotic effect of ECH on bone metabolism in the ovariectomized (OVX) rat model of osteoporosis in vivo.. Fifty-six aged 6 months female Sprague-Dawley rats were randomly assigned into sham-operated group (SHAM) and six OVX subgroups (n=8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), Xian-ling-gu-bao (XLGB, 0.5 g/kg body weight/day, orally), 17β-estradiol (E2, 50 μg/kg body weight/day, orally) or ECH (30, 90, and 270 mg/kg body weight, daily, orally) for 12 weeks respectively. We evaluated the pharmacological effects of E2, XLGB and ECH against osteoporosis by evaluating the body weight, uterus wet weight, serum and urine biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone histomorphology and uterus immunohistochemistry.. In OVX rats, the increases of body weight, serum hydroxyproline (HOP) levels, and the decreases of uterus wet weight and BMD were significantly reversed by ECH treatment. Moreover, three dosages of ECH completely corrected the increased urine concentration of calcium (Ca), inorganic phosphorus (P), and HOP observed in OVX rats. Furthermore, Micro-CT analysis results of distal femur showed that all ECH-treated groups notably enhanced bone quality compared to OVX group (p<0.05). Consistent with this finding, total femur BMD and biomechanical strength of tibia were significantly improved (p<0.05) after 12 weeks ECH administration. Histological results also showed the protective activity of ECH through promotion of bone formation and suppression of bone resorption. In addition, the ECH administration also significantly enhanced the expression of ER in the uteri according to immunohistochemical evaluation (p<0.05). Those findings, based on the serum and urine biochemical, BMD, Micro-CT, biomechanical test, histopathological and immunohistochemical parameters, showed that ECH has a notable antiosteoporotic effect, similar to estrogen, especially effective for prevention osteoporosis induced by estrogen deficiency.. These results suggest that ECH, as a new class of phytoestrogen, has a remarkable antiosteoporotic activity, and may be a promising candidate for treatment of postmenopausal osteoporosis induced by estrogen deficiency in a natural way through herbal resources.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Bone Density Conservation Agents; Calcium; Cistanche; Drugs, Chinese Herbal; Estradiol; Estrogens; Female; Glycosides; Hydroxyproline; Organ Size; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Plant Extracts; Plant Stems; Random Allocation; Rats; Rats, Sprague-Dawley; Uterus

Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms. Previous work showed that C. comosa extracts protect mice from ovariectomy-induced osteopenia with minimal effects on reproductive organs, and identified the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the major active component of C. comosa rhizomes. At 1-10μM, DPHD increased differentiation in transformed mouse osteoblasts, but the effect of DPHD on normal bone cells was unknown. We examined the concentration dependency and mechanism of action of DPHD relative to 17β-estradiol in nontransformed human osteoblasts (h-OB). The h-OB were 10-100 fold more sensitive to DPHD than transformed osteoblasts: DPHD increased h-OB proliferation at 10nM and, at 100nM, activated MAP kinase signaling within 30 min. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10nM, and optimal response in most cases was at 100 nM. At 7-21 days, DPHD accelerated osteoblast differentiation, indicated by alkaline phosphatase activity and osteoblast-specific mRNA production. Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780. During differentiation, DPHD promoted early expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including COL1A1 and osteocalcin comparably to 17β-estradiol. In h-OB, DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10nM 17β-estradiol. We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations, making it a promising compound to protect bone in menopausal women.

Topics: Cell Differentiation; Cell Proliferation; Curcuma; Diarylheptanoids; Estradiol; Female; Heptanol; Humans; MAP Kinase Signaling System; Menopause; Osteoblasts; Osteocalcin; Osteoporosis; Osteoprotegerin; Phytoestrogens; Plant Extracts; RANK Ligand; Rhizome; RNA, Messenger

Several studies have shown that soy isoflavones have estrogen-like activities and might constitute an alternative to hormone replacement treatment. The present study investigated the effects of soy isoflavones alone and combined with vitamin D3 on prevention of bone loss.. Sprague-Dawley rats were sham-operated (n = 8) or ovariectomized (OVX; n = 40), and then the OVX rats were randomly assigned to five groups that were untreated or treated for 14 wk with vitamin D3, 17β-estradiol, soy isoflavone extract (SIE), or vitamin D3 plus SIE. The effects of the isoflavones and 1α,25(OH)(2)D(3) on cultured osteoblasts and osteoclasts also were investigated.. In OVX rats, the bone mineral density and trabecular bone volume loss were improved by 17β-estradiol, SIE, or SIE plus vitamin D3 treatment. SIE treatment was more effective than vitamin D3 or 17β-estradiol in inhibiting increases in serum tumor necrosis factor-α levels and osteoblast osteoprotegerin expression. SIE plus vitamin D3 was more effective in increasing osterix expression than each alone. Bone cell cultures showed that the isoflavones induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. Isoflavones inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast resorption. The combination of isoflavones plus 1α,25(OH)(2)D(3) showed additive effects on the increase in cell proliferation of cultured preosteoblasts.. Treatment with soy isoflavones might be an alternative to hormone replacement therapy in decreasing bone loss from postmenopausal estrogen deficiency. In addition, there are further effects on increasing transcription factor osterix expression and preosteoblast proliferation when these were combined with vitamin D3.

Topics: Alkaline Phosphatase; Animals; Bone Density; Cholecalciferol; Disease Models, Animal; Drug Synergism; Estradiol; Female; Glycine max; Humans; Interleukin-1beta; Isoflavones; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tumor Necrosis Factor-alpha

Topics: Animals; Antioxidants; Bone and Bones; Catechin; Dietary Supplements; Estrogens; Female; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens

Drynaria fortunei (Kunze) J. Sm. (DF), a Chinese herb commonly used for the treatment of bone fracture, was previously shown to exert anabolic effects on bone. However, its active ingredients as well as the mechanisms of action are far from clear. The present study aimed to characterise the bone anabolic effects of DF flavonoid fraction (DFTF) in ovariectomised (OVX) mice and to determine if DFTF and its isolated compounds exert oestrogen-like effects in rat osteoblast-like UMR-106 cells. Young OVX C57/BL6J mice were treated orally with DFTF (0·087, 0·173 or 0·346 mg/g per d), 17b-oestradiol (2 mg/g per d) or its vehicle for 6 weeks. Serum and urine samples were collected for biochemical marker analysis. Bones were collected for computed tomography analysis. UMR-106 cells were treated with DFTF and isolated compounds naringin, (2S)-5,7,30,50-tetrahydroxy-flavonone 7-O-neohesperidoside (compound 1) and 5,7-dihydroxychromone 7-O-neohesperidoside (compound 2). DFTF exerted dose-dependent effects in improving bone mineral densities as well as bone strength at the femur, tibia and lumbar spine L1 in OVX mice. DFTF and the three isolated compounds stimulated osteoblastic cell proliferation and alkaline phosphatase activities in a dose-dependent manner. In addition, they stimulated the ratio of osteoprotegrin and receptor-activator NF-kB ligand mRNA expression, suggesting their involvement in inhibiting osteoclastogenesis. These stimulatory effects on osteoblastic functions were abolished in the presence of oestrogen receptor (ER) antagonist, ICI 182780. The present results suggested that DFTF is effective in protecting against OVX-induced bone loss in mice, and its actions in regulating osteoblastic activities appear to be mediated by ER.

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Density Conservation Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Estradiol; Female; Femur; Flavanones; Flavonoids; Fulvestrant; Lumbar Vertebrae; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoclasts; Osteoporosis; Osteoprotegerin; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Polypodiaceae; Rats; RNA, Messenger; Tibia

Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats.. Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17β-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning.. Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects.. ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

Topics: Animals; Cicer; Estradiol; Female; Femur; Follicle Stimulating Hormone; Immunohistochemistry; Isoflavones; Luteinizing Hormone; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Extracts; Rats; Rats, Sprague-Dawley; Seedlings; Uterus

Daidzein (Daid) has been implicated in bone health for its estrogen-'like' effects but low bioavailability, unfavorable metabolism and uterine estrogenicity impede its clinical potential. This study was aimed at assessing isoformononetin (Isoformo), a naturally occurring methoxydaidzein, for bone anabolic effect by overcoming the pitfalls associated with Daid.. Sprague-Dawley ovariectomized (OVx) rats with established osteopenia were administered Isoformo, 17β-oestradiol (E2) or human parathyroid hormone. Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labeling of bone. Osteoblast apoptosis was measured by co-labeling of bone sections with Runx-2 and TUNEL. Biochemical markers of bone metabolism were measured by ELISA. Plasma and bone marrow levels of Isoformo and Daid were determined by LC-MS-MS. Rat bone marrow stromal cells were harvested to study osteoblastic differentiation by Isoformo and Daid. New born rat pups were injected with Isoformo and Daid to study the effect of the compounds on the expression of osteogenic genes in the calvaria by real time PCR.. In osteopenic rats, Isoformo treatment restored trabecular microarchitecture, increased new bone formation, increased the serum osteogenic marker (procollagen N-terminal propeptide), decreased resorptive marker (urinary C-terminal teleopeptide of type I collagen) and diminished osteoblast apoptosis in bone. At the most effective osteogenic dose of Isoformo, plasma and bone marrow levels were comprised of ~90% Isoformo and the rest, Daid. Isoformo at the concentration reaching the bone marrow achieved out of its most effective oral dosing induced stromal cell mineralization and osteogenic gene expression in the calvaria of neonatal rats. Isoformo exhibited uterine safety.. Our study demonstrates that Isoformo reverses established osteopenia in adult OVx rats likely via its pro-survival effect on osteoblasts. Given its bone anabolic and anti-catabolic effects accompanied with safety at uterine level we propose its potential in the management of postmenopausal osteoporosis.

Topics: Animals; Apoptosis; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Bone Diseases, Metabolic; Bone Resorption; Calcification, Physiologic; Female; Isoflavones; Metabolism; Osteoblasts; Osteogenesis; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Stromal Cells; Uterus

We compared the effects of the S-enantiomer and racemic forms of equol on bone using ovariectomized (OVX) mice. Femoral bone mineral density and bone strength decreased in the OVX mice, but not in OVX mice administered 0.5 mg/d S-equol. This, however, did not hold for racemic equol. Serum and urine S-equol concentrations were higher in the mice administered S-equol than in those administered racemic equol. These results suggest that the inhibitory effects of S-equol on bone fragility in OVX mice are greater than those of racemic equol.

Topics: Animals; Bone Density; Chromatography, High Pressure Liquid; Disease Models, Animal; Equol; Female; Femur; Humans; Mice; Osteoporosis; Osteoporotic Fractures; Ovariectomy; Phytoestrogens; Stereoisomerism

Miroestrol (MR) is a highly active phytoestrogen isolated from tuberous root of Pueraria candollei var. mirifica (PM). Modulatory effects of PM and MR on osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) mRNAs which are bone-specific genes were investigated in ovariectomized female ICR mice. After ovariectomy, expression of OPG mRNA was suppressed but that of RANKL was induced. Estradiol benzoate (E2) recovered OPG expression to the level comparable to the sham while that of RANKL was suppressed in ovariectomized mice. PM crude extract (PME) significantly down-regulated the expression of RANKL mRNA with no change in the OPG level whereas MR elevated the expression of OPG mRNA with lowering level of RANKL mRNA, resulting in the increased OPG/RANKL ratio, and consequently lead to lowering progression of osteoporosis at molecular level. These findings revealed potential of PME and MR on bone loss prevention via increasing the ratio of OPG to RANKL (osteoformation/osteoresorption) in liver of ovariectomized mice. Therefore, using PME and MR as alternative hormone replacement therapy of E2 might be beneficial recommended due to advantageous on regulation of osteoporosis related genes.

Topics: Animals; Bone and Bones; Bone Development; Female; Gene Expression Regulation; Mice; Mice, Inbred ICR; Osteoporosis; Osteoprotegerin; Ovariectomy; Phytoestrogens; Pueraria; RANK Ligand; Steroids

Prebiotics and phytoestrogens have sparked great interest because evidence indicates that the consumption of these dietary constituents leads to lower cholesterol levels and inhibition of postmenopausal bone loss. The aim of this study was to determine the effect of both a prebiotic (Synergy) and a phytoestrogen (genistein) on bone and blood lipid levels in an animal model of postmenopausal women.. A 4-week feeding study was conducted in 5-month-old ovariectomized (OVX) Sprague-Dawley rats to examine the effect of genistein, Synergy (a prebiotic), and genistein and Synergy combined on bone density and strength, calcium metabolism, and lipid biomarkers. There were six treatment groups: sham control, OVX control, OVX rats receiving daily estradiol injections, and OVX rats receiving an AIN-93M diet supplement with 200 ppm genistein, with 5% Synergy or with 200 ppm genistein and 5% Synergy combined.. The rats receiving genistein had significantly lower total serum cholesterol concentrations than OVX rats in the control group (17%), OVX rats receiving daily estradiol injections (14%), and OVX rats fed the 5% Synergy diet (19%). Consumption of Synergy improved calcium absorption efficiency (41%) compared with nonconsumption (OVX control). Sham control rats had a significantly higher femoral bone density, as determined by underwater weighing, than did the rats in all of the OVX groups. Genistein consumption restored total and trabecular bone mineral density at the distal femur similar to the levels of sham rats.. Genistein supplementation imparts modest heart health benefits and improves bone geometry at the distal femur, and prebiotic consumption (Synergy) results in improved calcium utilization strength in ovariectomized rats, but the combination produced no synergistic effects.

Topics: Animals; Bone and Bones; Bone Density; Calcium; Cholesterol; Drug Synergism; Female; Femur; Genistein; Osteoporosis; Ovariectomy; Phytoestrogens; Prebiotics; Probiotics; Random Allocation; Rats; Rats, Sprague-Dawley

Flaxseed, rich in the phytoestrogen lignan secoisolariciresinol diglycoside (SDG), provides protection against bone loss at the lumbar vertebrae primarily when combined with low-dose estrogen therapy in the ovariectomized rat model of postmenopausal osteoporosis. Whether SDG metabolites are accessible to skeletal tissue, and thus have the potential to interact with low-dose estrogen therapy to exert direct local action on bone metabolism, is unknown. The objective of this study was to determine whether metabolites of SDG are accessible to the skeleton of ovariectomized rats and to compare the distribution of SDG metabolites in skeletal tissue with that in other tissues. Rats were fed a 10% flaxseed diet and gavaged daily with tritium-labeled SDG (7.4 kBq/g of body weight) in deionized water (500 μL) (n=3) or deionized water alone (n=3) for 7 days, after which tissues were collected for liquid scintillation counting. Radioactivity was detected in similar concentrations in the lumbar vertebrae, femurs, and tibias. Compared with non-skeletal tissues, total radioactivity in the skeleton was significantly lower than in the liver, heart, kidney, thymus, and brain (P < .001). There were no significant differences in levels of radioactivity between skeletal tissue versus the spleen, lung, bladder, uterus, vagina, and mammary gland. In conclusion, SDG metabolites are accessible to skeletal tissue of ovariectomized rats. Thus, it is biologically plausible that SDG metabolites may play a direct role in the protective effects of flaxseed combined with low-dose estrogen therapy against the loss of bone mass and bone strength in the ovariectomized rat model of postmenopausal osteoporosis.

Topics: Animals; Butylene Glycols; Disease Models, Animal; Female; Femur; Flax; Lignans; Lumbar Vertebrae; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Tibia

Curcuma comosa Roxb. or Wan chak motluk is an indigenous medicinal herb and has traditionally been used among postmenopausal women for relief of unpleasant menopausal symptoms.. Estrogen deficiency is a causative factor in the development of osteoporosis in menopausal women. Phytoestrogens, non-steroidal plant-derived compounds which have an array of beneficial effects, are considered as an effective alternative compound in preventing bone loss caused by the deficiency of estrogen. The present study determined the potential effect of Curcuma comosa Roxb. (C. comosa) hexane extract containing phytoestrogens in protecting bone loss induced by ovariectomy in mice.. Mature Swiss albino female mice were ovariectomized and treated with the C. comosa extract for 5 weeks. Bone calcium content, bone mass density, histology, and bone markers were evaluated.. The ovariectomized mice showed a marked decrease in total bone calcium content and bone mass density of lumbar vertebrae 5-6, femur and tibia bone in comparison with the intact control mice. Bone histology demonstrated the poor development of endochondral bone formation in ovariectomized mice which correlated with a decrease in plasma bone alkaline phosphatase activity. Treatment with C. comosa protected against the loss of total bone calcium content and bone mass density in both trabecular and cortical bones, similar to results observed with estrogen treatment. In addition, C. comosa treatment resulted in less increase in uterine weight compared to estrogen treatment.. Our results suggest that C. comosa prevents bone loss induced by estrogen deficiency. Therefore, C. comosa would be a potential alternative treatment for prevention of postmenopausal osteoporosis.

Topics: Absorptiometry, Photon; Animals; Bone Density; Calcium; Curcuma; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Femur; Lumbar Vertebrae; Mice; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Extracts; Tibia; Uterus

This experiment established the ovariectomized (OVX) rat model of postmenopausal osteoporosis and examined the effect of the oral administration of different dosages of dioscorea, red mold dioscorea (RMD), and soy isoflavones on bone mineral density (BMD). Three months after osteoporosis had been induced and 4 weeks after feeding had begun, the tibia and femur BMD of OVX rats administered RMD showed significant increases compared with that of all other groups of OVX rats. Closer examination using microcomputed tomography also revealed that the RMD-administered rats had denser trabecular bone volume and a higher trabecular number compared to all other rat groups. Reconstructed 3D imaging indicated increases in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in OVX rats. These findings indicate that administration of monacolin K and phytoestrogen diosgenin could prevent bone loss induced by estrogen deficiency.

Topics: Animals; Bone Density; Dioscorea; Diosgenin; Disease Models, Animal; Female; Fermentation; Flavins; Glycine max; Heterocyclic Compounds, 3-Ring; Isoflavones; Lovastatin; Monascus; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Roots; Rats; Rats, Sprague-Dawley

To evaluate the effects of different doses of phytoestrogen (genitein) combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized (OVX) mice.. 63 female CD-1 mice, 29g average weight, were randomly divided into 7 groups. Including Sham group, OVX group and groups of treatment with calcium, vitamin D3 and genistein in high dose (GH, 67 mg/kg), genistein in moderate does (GM, 33.5 mg/kg), genistein in low dose(GL,16.75 mg/kg), pure genistein (G) and pure 17-betaestradiol (E2). After six weeks treatment, bone mineral density (BMD), bone mineral content (BMC), Biomechanical characteristics bone strength and bone biochemical markers were measured in all mice.. In the groups of GH, GM and GL, it was stimulative effect of genistein on elevating uterine weight in ovariectomized mice and the effect in GL group is lower. BMD, BMC, length and width of femora were significantly increased in GM group mice than those in OVX mice (P < 0.01), as well as BMD of femora in GL group mice were markedly increased (P < 0.01). Peak load and resilience of femora were the most conspicuously increased in GL group mice than those in others treatment group mice (P < 0.01). In GL group, bone alkaline phosphatase (BALP) increased and tartrate-resistant acid phosphatase (TRAP) decreased (P < 0.01).. It was lower stimulative effect of low dose of phytoestrogen (genitein) combined with calcium and vitamin D3 on elevating uterine weight in ovariectomized mice. Low dose of Phytoestrogen (genistein) combined with calcium and vitamin D3 might increase BMD, improve the mechanical strength of bone, promote bone fromation and inhibit bone resorption significantly. It might reduce the dose of genistein administrated and be safter than E2.

Topics: Animals; Bone Density; Calcium; Cholecalciferol; Drug Therapy, Combination; Female; Genistein; Mice; Mice, Inbred ICR; Osteoporosis; Ovariectomy; Phytoestrogens

Hot flashes are a common and distressing symptom of menopause, affecting approximately 62-83% of women undergoing the menopausal transition. Several pharmacologic treatments for hot flashes, including hormone replacement therapy (HRT) have been shown to reduce the frequency and intensity of hot flashes. However, some women prefer not to use HRT and seek alternative treatments, such as phytoestrogens. Feminorm, Feminorm Duo and Feminorm good night have a beneficial effect on vasomotor symptoms, depression, osteoporosis and cardio-vascular diseases.

Topics: Depression; Female; Hot Flashes; Humans; Menopause; Osteoporosis; Phytoestrogens; Plant Extracts; Trifolium

Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as well as some other nonhepatic indications have been reported. Therefore, more attention should be paid for the hormonal side effects of SIL. Since the available data on the possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and body weight were measured in all animals. Biochemical markers of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin), endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological examination. In addition, the binding property of SIL to the two estrogen receptors (ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in protection of trabecula thickness, decreased serum levels of ALP and increased serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived in the present study presented an overview of SIL many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative effects in uterus. The observed effects may be due to additive beneficial effect of SIL on bone either due to direct interaction with ERbeta or increasing bone formation parameters including calcium, phosphorus, osteocalcin and PTH.

Topics: Alkaline Phosphatase; Animals; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Calcium; Endometrial Hyperplasia; Estradiol; Estrogen Receptor beta; Ethinyl Estradiol; Female; Hormones; Lipids; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Selective Estrogen Receptor Modulators; Silybum marianum; Silymarin; Uterus; Weight Gain

The technology of gene manipulation is often used in mice. A crucial point for osteoporosis research is the evaluation of biomechanical and morphologic parameters. These parameters, however, are difficult to measure in mice. Nevertheless, this study demonstrates the capability of using techniques for the evaluation of bone quality and quantity after various treatments in osteopenic mice. After ovariectomy, 60 C57BL/6J mice were divided into 4 groups and were fed a soy-free diet (C) supplemented with estradiol, genistein or equol for 3 months. To analyze the osteoprotective effects of the tested supplements, we evaluated the bone biomechanical properties, histomorphometric changes and bone mineral density of the proximal tibiae metaphysis. The biomechanical parameters of genistein (GEN) were shown to be similar to those levels observed with estradiol (E). The biomechanical parameters of both GEN and E were significantly superior to those observed with C. Supplementation with equol (EQO) demonstrated higher mean biomechanical values than those observed with C. The histomorphometric evaluation demonstrated an increased number of nodes in mice treated with GEN and E as compared to the mice treated with EQO and C. Treatment with E and EQO led to improved cortical bone, which was only partly seen with the mice treated with GEN. The analysis of the bone mineral density (BMD) demonstrated that treatment with GEN and E resulted in a significant improvement as compared to the mice treated with C, while the cancellous density was significantly increased in all of the supplementation groups. This study conclusively demonstrated that bone quality and quantity parameters can be measured in mice. Furthermore, biomechanical and morphologic evaluations were shown to be reliable for use in mice. Further studies may combine these techniques with gene manipulation technology to better understand osteoporosis. Treatment with GEN resulted in improved biomechanical results and enhancement of morphologic parameters.

Topics: Animals; Biomechanical Phenomena; Bone Density; Bone Density Conservation Agents; Equol; Estradiol; Female; Genistein; Isoflavones; Mice; Mice, Inbred C57BL; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Tibia

We have reported that soy isoflavones are capable of preventing loss of bone mineral density (BMD) in rats due to ovariectomy. The intestinal microflora is important in rendering soy isoflavones bioavailability by facilitating their conversion to equol. Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones. The purpose of this study was to examine whether combination of genistin and fructooligosaccharides (FOS), a prebiotic, can enhance the effects of soy isoflavones on bone in ovariectomized (OVX) female rats. Forty-eight 90-day-old female Sprague-Dawley rats were either sham-operated (Sham; one group) or Ovx (three groups) and were placed on dietary treatment for 50 days. The Sham and one Ovx group received a control diet, and the remaining Ovx groups received genistin-rich isoflavones diet (Ovx+G) or genistin-rich isoflavones and FOS diet (Ovx+G+FOS). After 50 days, blood and bone specimens were collected for analysis. The genistin-rich isoflavones diet was able to significantly increase the whole-body, right femur, and fourth lumbar BMD by 1.6%, 1.48%, and 1.3%, respectively in comparison with the Ovx control. The combination of genistin-rich isoflavones diet and 5% FOS further increased whole-body, right femur, and fourth lumbar BMD more compared to the genistin-rich isoflavones diet. Our findings suggest that although a genistin-rich isoflavones diet can increase the BMD in rats with Ovx-induced bone loss, combination of genistin-rich isoflavones and FOS had greater effect in preventing bone loss in this rat model.

Topics: Animals; Bone and Bones; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Estrogens; Female; Glycine max; Intestines; Isoflavones; Oligosaccharides; Osteolysis; Osteoporosis; Ovariectomy; Ovary; Phytoestrogens; Phytotherapy; Plant Extracts; Prebiotics; Rats

Plant-derived estrogen-like compounds such as isoflavones (IF) especially daidzein and genistein are said to be preserving the bone in the osteoporotic conditions. However, it is not known whether a combination of IF and calcium (Ca) supplementation attenuates losses in bone mass and prevents the loss of vitamin D (VD). The present study addresses the role of phytoestrogens (PE) and Ca supplementation in low Ca and low VD diet induced osteoporosis (OSP). Cowpea (CP) which has high amount of the IF was selected to study its effect on diet induced osteoporotic conditions. Female weanling WNIN rats (total of 68) were divided into five groups and fed for five weeks on semisynthetic diet with low Ca (0.15%) and low VD (0.1IU/day/rat) in combination with low (10 mg/kg) or high (25 mg/kg) concentrations of PEs derived from CPIF. The study groups are: (I) normal Ca(0.47%) and normal VD (25IU/day/rat), (II) low Ca+low VD, (III) low Ca+low VD+low CPIF (10 mg/kg diet), (IV) low Ca+low VD+high CPIF (25 mg/kg diet) and (V) low Ca+low VD+17-(-estradiol (3.2 mg/kg diet). After the development of OSP the group II was subgrouped into: (SG I) continued on low Ca+VD, (SG II) low CPIF, (SG III) high CPIF, (SG IV) 17-beta-estradiol and (SG V) normal Ca and VD. Serum 25-VD levels were in the range of 14-38 ng/ml in groups I, III, IV and V, where as the values were very low in the group II (5.8 ng/ml). These were partially reversed upon supplementation of CPIF. The results correlated with altered Ca levels, body weight, bone mineral density and content and other related biochemical parameters. The paper further explains the possibility of protective and therapeutic role of VD in the presence of CPIF in osteoporotic health manifestations.

Topics: Animals; Bone Density; Calcium; Cholecalciferol; Dietary Supplements; Disease Models, Animal; Female; Genistein; Isoflavones; Osteoporosis; Phosphorus; Phytoestrogens; Plants; Rats; Vitamin D

Administration of the isoflavone genistein (GEN) has been described to result in bone protection but also to induce uterotrophic responses. To compare bone protective effects of GEN with an isoflavone-rich diet (IRD) and to further elucidate molecular mechanisms involved in bone-protection, ovariectomized rats (OVX) received either a diet low in isoflavone content (IDD) enriched with GEN (42 mg kg(-1)b.wtd(-1)) (GEN(d)), an IRD (14 mg kg(-1)b.wtd(-1) GEN, 14 mg kg(-1)b.wtd(-1) daidzein) or were treated subcutaneously (s.c.) with GEN (10 mg kg(-1)b.wtd(-1)) (GEN(sc)) for 12 weeks. Intact (SHAM), vehicle treated OVX animals and those substituted with 17beta-estradiol (2microg kg(-1)b.wtd(-1)) (E(2)), served as controls. OVX-induced bone loss could be antagonized in E(2), GEN(sc), GEN(d) and IRD groups. Uterine wet weight (UWW) was only stimulated in E(2) and GEN(sc) animals. Serum biomarkers of bone-formation (osteocalcin, osteopontin) and bone-resorption (telopeptides of collagen type I, pyridinoline cross-links) were elevated in OVX compared to SHAM and E(2) animals. Feeding IRD stimulated bone-formation and inhibited bone-resorption, whereas s.c. or dietary administration of GEN only resulted in a stimulation of bone-formation. The results of the present study indicate that in contrast to s.c. administration, dietary intake of GEN resulted in bone protection without stimulation of UWW. Dietary intake of isoflavones by an IRD also did not result in a stimulation of UWW, yet IRD appeared to be more effective in bone protection than administration of pure GEN.

Topics: Animals; Bone Density; Bone Density Conservation Agents; Bone Resorption; Collagen Type I; Diet; Disease Models, Animal; Estradiol; Female; Genistein; Injections, Subcutaneous; Organ Size; Osteocalcin; Osteogenesis; Osteopontin; Osteoporosis; Ovariectomy; Peptides; Phytoestrogens; Rats; Rats, Wistar; Tibia; Uterus

Osteoporosis research undertaken in males is rare and there are only a few therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis. Sixty 3-month-old male rats were orchidectomized and divided into five groups. The groups either received soy-free food (C), estradiol (E), testosterone (T) or Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The tibia metaphysis was tested biomechanically and histomorphometrically. The AC high group reached 87% of the biomechanical values of the estradiol group and was significantly superior to the control group. Testosterone supplementation resulted in poor biomechanical properties. The cortical bone parameters of the AC group were similar to the control group, while supplementation with estradiol and testosterone demonstrated a reduction of cortical bone. The AC high group reached 88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number of trabecular nodes compared with estradiol supplementation. Vitex agnus castus demonstrated osteoprotective effects in males. It preserves the cortical as well as the trabecular bone and might be a safe alternative for HRT. Testosterone supplementation has positive effects on trabecular bone, which are concurrently counteracted by the loss of cortical bone.

Topics: Animals; Biomechanical Phenomena; Bone Density; Bone Density Conservation Agents; Estradiol; Male; Orchiectomy; Osteoporosis; Phytoestrogens; Phytotherapy; Rats; Rats, Sprague-Dawley; Tensile Strength; Testosterone; Tibia; Vitex

Hypo-estrogenism during menopause is the cause of numerous disturbances affecting various structures such as the oral cavity which can present with the following symptoms: changes in salivary secretion, gingivitis, bleeding and altered taste sensation. The object is to study whether hormone replacement therapy prescribed for female patients in menopause have any beneficial effect on the oral discomfort which affects the quality of life of these patients.. The study enrolled 95 female patients; 14 were the control group and received no hormone replacement therapy while 81 patients underwent two types of therapy: 38 were prescribed estrogen therapy and 43 phytotherapy. The main outcome measures were alterations of the oral cavity: salivary change, gingivitis, bleeding and taste changes.. It was observed that the patients receiving treatment had an improvement or disappearance of symptoms in the oral cavity and that estrogen was more effective than phytotherapy regarding the salivary change while the gingivitis, bleeding and taste changes was the same for both therapies.. Estrogen and phytotherapy have beneficial effect on oral discomfort in women in menopause. The proposed treatment can have a beneficial effect on osteopenia and osteoporosis and therefore also on possible increase of future tooth loss during menopause.

Topics: Case-Control Studies; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Genistein; Gingivitis; Humans; Menopause; Middle Aged; Mouth Diseases; Mouth Mucosa; Osteoporosis; Phytoestrogens; Phytotherapy; Quality of Life; Saliva; Secretory Rate; Taste Disorders; Treatment Outcome

Healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Hormone replacement therapy could improve fracture healing, but, because of its potential side effects, natural alternatives are more appealing. The aim of this study was to determine if the soy metabolite equol and the native isoflavone genistein, in comparison to 17beta-estradiol, improve metaphyseal fracture healing in ovariectomy-induced osteoporotic bone of the rat. Forty-eight 12-week-old female rats developed severe osteoporosis ten weeks after ovariectomy. After metaphyseal tibial osteotomy and standardized stable internal fixation, changes in callus morphology were evaluated biomechanically, qualitatively and quantitatively in fluorochrome-labeled histological sections and microradiographs in ovariectomized rats (C) and under standardized 17beta-estradiol (E), equol (EQ) and genistein (G) supplemented rats over a period of five weeks. Estrogen and equol were able to improve the elasticity of callus formation significantly in postmenopausal osteoporotic bone (stiffness of C: 121.40 +/- 47.08 N/mm, E: 147.90 +/- 39.38 N/mm, EQ: 167.8 +/- 59.90 N/mm). The effects of estrogen were more anabolic than those of equol and were visible in changes to the trabecular bone (N.Nd of E: 6.47 +/- 7.68, EQ: 4.25 +/- 3.96). However, in terms of the whole body, equol seemed to induce less of an adverse reaction than estrogen (body weight of C: 342.20 +/- 19.91 g, E: 280.25 +/- 12.05 g, EQ: 308.75 +/- 24.28 g). Genistein as an osteoclast inhibitor influenced callus stiffness (G: 144.50 +/- 61.52 N/mm) and negatively impacted trabecular structure (N.Nd of G: 0.59 +/- 1.01) in severely osteoporotic bones. Estrogen and equol were able to improve fracture healing in ovariectomy-induced osteoporotic bones, and the extent of callus formation played only a minor role. Genistein rather negatively influenced fracture healing. The metaphyseal osteotomy model in ovariectomized rats allows an accurate study of the therapeutic effects of antiosteoporotic substances on the fracture healing process.

Topics: Animals; Bony Callus; Disease Models, Animal; Elasticity; Equol; Estradiol; Estrogens; Female; Fracture Healing; Genistein; Glycine max; Isoflavones; Osteoclasts; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Tibia

Soy isoflavone preparations, such as purified genistein and a soy extract (Novasoy), were reported previously to exert beneficial effects on bones. Our purpose in this study was to compare the effects of genistein and Novasoy on 3-dimensional trabecular bone parameters and the expression of bone-specific genes in ovariectomized (OVX) mice. The sham-operated mice were fed the control diet and OVX mice were fed diets containing genistein or Novasoy or the control diet, with or without 17beta-estradiol treatment, for 5 wk. Trabecular bone parameters of tibias were measured by microcomputed tomography and gene expression was assayed by real-time PCR. Consumption of diets containing genistein or Novasoy partially prevented the ovariectomy-induced increase in body weight but did not alter the uterus weight of the OVX mice. Novasoy, but not purified genistein, significantly preserved trabecular bone mass, bone volume, and trabecular bone separation in the proximal tibial metaphysis. Purified genistein decreased mRNA expression of receptor activator of nuclear factor-kappaB ligand (RANKL), carbonic anhydrase II, and cathepsin K and enhanced the ratio of osteoprotegrin:RANKL mRNA expression in the tibial head of the OVX mice. In contrast, the diet containing Novasoy suppressed the OVX-induced increase in serum alkaline phosphatase but did not alter bone-specific gene expression of tibia. Our study demonstrated that a soy extract containing a similar level of genistein in the form of Novasoy is more effective than purified genistein in improving tibial trabecular bone quality in OVX mice, but the mechanism of action might be distinct from that of genistein.

Topics: Animals; Bone and Bones; Carbonic Anhydrase II; Cathepsin K; Female; Gene Expression Regulation; Genistein; Mice; Mice, Inbred C57BL; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Extracts; RANK Ligand; RNA, Messenger; Soy Foods; Specific Pathogen-Free Organisms; Weight Gain

Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.. Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.. Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.. The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.

Topics: Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Estradiol; Female; Genistein; Osteoporosis; Ovariectomy; Phytoestrogens; Raloxifene Hydrochloride; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors

To find a more potent alternative with less oestrogen-related side effects for hormone replacement therapy (HRT) in postmenopausal osteoporosis, we designed and synthesized a NO-releasing prodrug of genistein (NO-G) according to the structure of NONSAIDs. The purpose of this study was to evaluate the effects of the prodrug on bone in ovariectomised (OVX) rats.. Forty-eight adult Sprague-Dawley female rats were ovariectomised and treated with vehicle, 9 mg/kg genistein and 4.5, 9 or 18 mg/kg NO-G by oral administration daily. The bioassays were performed in terms of bone mineral density (BMD), mechanical testing, bone formation markers, bone alkaline phosphatase (b-ALP) and osteocalcin (OCN) and bone resorption marker urine deoxypyridinoline (DPD). In addition, the effects of the drugs on uterus and body weight were examined.. After treatment for 12 weeks, the BMD of whole femur and tibia in the NO-G (9 and 18 mg/kg) groups were 12.1% and 12.2% higher than that of OVX group (P<0.01); the bending strength of the femur was 11.2% and 12.2% higher than OVX group (P<0.01). The OVX-induced increase of serum b-ALP, OCN and urinary DPD were markedly attenuated. The prodrug showed no side effects on uterus and body weight.. The NO-releasing prodrug of genistein improves the bone loss in OVX rats without stimulatory effects on the uterus, which suggests that the product could potentially be used for the prevention and treatment of postmenopausal osteoporosis.

Topics: Administration, Oral; Animals; Body Weight; Bone Density; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Genistein; Nitric Oxide; Osteoporosis; Ovariectomy; Phytoestrogens; Prodrugs; Rats; Rats, Sprague-Dawley; Treatment Outcome

To investigate the preventive effect of epimedium-derived phytoestrogen (PE) on osteoporosis induced by ovariectomy (OVX) in rats, 11-month-old female Wistar rats were randomly divided into Sham, OVX and PE groups. One week after OVX, daily oral administration of PE (0.4 g.kg(-1).day(-1)) started in PE group, and rats in Sham and OVX groups were given vehicle accordingly. The administrations lasted for 12 weeks. The biological markers including serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) for bone turnover were evaluated at the end of the 12th week. On the 13th week, all the rats were sacrificed. The right proximal tibiae were removed, subjected to micro CT for determination of trabecular bone structure and then bone histomorphometry was performed to assess bone remodeling. The OVX rats were in a high bone turnover status as evidenced by increased bone formation markers and bone resorption markers. Treatment with PE could suppress the high bone turnover rate in OVX rats. Micro CT data revealed that PE treatment could ameliorate the deterioration of the micro-architecture of proximal tibiae induced by OVX, as demonstrated by greater bone volume, increased trabecular thickness and less trabecular separation in PE group in comparison with OVX group. The static and dynamic parameters of bone histomorphometry indicated that there were significant increases in bone formation variables and significant decreases in bone resorption variables between PE and OVX groups. The findings suggest that PE has a beneficial effect on trabecular bone in OVX rat model and this effect is possibly associated with stimulation of bone formation as well as inhibition of bone resorption.

Topics: Animals; Bone and Bones; Bone Remodeling; Epimedium; Female; Osteogenesis; Osteoporosis; Ovary; Phytoestrogens; Rats; Rats, Wistar; Tibia; Tomography, X-Ray Computed

Estrogens and estrogen-like substances have been reported to play an important role in male bone homeostasis and to prevent bone loss. Pueraria mirifica (Leguminosae), a Thai herbal plant, containing a high amount of phytoestrogens was a choice of interest for this study. We examined the effects of crude P. mirifica on bone loss and influences on reproductive organs in male rats.. Using fully mature and orchidectomized (ORX) rats, the effects of 0, 10, 100 and 1000 mg/kgB.W./day of P. mirifica and 0.1mg/kg B.W./day of 17 alpha-ethinylestradiol (a positive control) were evaluated on bone mineral density (BMD) and bone mineral content (BMC) measured with a peripheral Quantitative Computerized Tomography (pQCT) densitometry.. Bone loss in trabecular and cortical bones of the various sites of axial bone (fourth lumbar vertebral body) and long bones (tibia and femur) after ORX was dose-dependently prevented by P. mirifica. The effects were specific on bone types and sites. The weights of the accessory sex organs, seminal vesicle and ventral prostrate gland, which significantly decreased after 3-month of ORX, were not altered by P. mirifica.. The results suggest that P. mirifica treatment may be useful to prevent an osteoporosis in elderly hypogonadism subjects without influences on reproductive organs.

Topics: Animals; Bone and Bones; Bone Density; Dose-Response Relationship, Drug; Male; Orchiectomy; Osteoporosis; Phytoestrogens; Phytotherapy; Plant Preparations; Prostate; Pueraria; Rats; Rats, Sprague-Dawley; Seminal Vesicles

Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor.. A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 microg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 mug/g body weight/d, simultaneously with short-chain FOS (Actilight, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX.. Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant.. In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.

Topics: Animals; Biomarkers; Body Weight; Bone Density; Bone Resorption; Disease Models, Animal; Equol; Female; Femur; Genistein; Glycine max; Isoflavones; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Wistar; Uterus

This study was to examine whether skeletal health deterioration in the hypogonadal situation is a consequence of an alteration in the functional status of peripheral mononuclear cells and its amelioration, if any, by an oil extract of garlic. The results suggest that hypogonadism-induced oxidative stress of peritoneal macrophages and lymphocytes could be reduced by supplementation with an oil extract of garlic. However, estrogen deficiency did not cause any significant change in DNA fragmentation of peritoneal macrophages. The hypogonadism-induced increase in the serum levels of IL-6 and TNF-alpha were significantly reduced by an oil extract of garlic. Further, such supplementation could revive the hypogonadism-induced decrease in serum estrogen titer and counter-balance the increase in bone turnover as determined by low bone tensile strength and alterations in bone related biochemical variables such as urinary calcium, hydroxyproline, calcium to creatinine ratio and serum tartrate resistant acid phosphatase activity (TRAP). The garlic oil supplemented partial recovery of the serum estrogen titer in hypogonadal rats was found to be persistently associated with reduced oxidative stress of peritoneal macrophages and lymphocytes, reduced serum interleukins and better preservation of bone mass. This study proposes that the hypogonadism-induced bone loss has a direct correlation with the functional status of lymphocytes and peritoneal macrophages, and garlic can prevent this.

Topics: Acid Phosphatase; Allyl Compounds; Animals; Catalase; Disulfides; DNA Fragmentation; Estradiol; Female; Femur; Garlic; Interleukin-6; Lipid Peroxidation; Lymphocytes; Macrophages, Peritoneal; Nitrites; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Superoxide Dismutase; Tensile Strength; Tumor Necrosis Factor-alpha

The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological and molecular analyses on reproductive organs. The impact on the oxidative metabolism of estradiol and on associated cytochrome P450 (CYP) activities was evaluated in liver microsomes. The relative wet weights of both the uterus and the vagina were increased in the equol group, but no significant changes in proliferating cell nuclear antigen or hormone receptor mRNA expression were noticed. In contrast, genistein and daidzein did not induce uterotrophy but caused an overexpression of estrogen receptor alpha mRNA which could correspond to a long-lasting effect of physiological concentrations of estrogens. The hepatic metabolism of estradiol was influenced by daidzein which increased the synthesis of putative mutagenic derivatives. At the same time, genistein favored estrogen 2-hydroxylation, and equol decreased 4-hydroxyestrogen production. Surprisingly, no significant alteration in hepatic CYP activities was detected. Taken together, these results demonstrate that isoflavonoid-based bone-sparing treatments are able to cause side effects on other estrogen-sensitive target organs when given in the long-term.

Topics: Animals; Bone Density; Cytochrome P-450 Enzyme System; Disease Models, Animal; Equol; Estradiol; Female; Gene Expression Regulation; Genistein; Isoflavones; Menopause; Microsomes, Liver; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Uterus; Vagina

Oestrogen deficiency leads to a considerable bone loss, thus, osteopenia and osteoporosis are serious complications after menopause.. To evaluate the effects of a daidzein metabolite equol on bone mass density (BMD) and markers of bone remodelling in an ovariectomized (ovx) rat model of postmenopausal bone loss and compare them with the effects of 17beta-estradiol.. Twenty-eight female Sprague-Dawley rats were ovx and fed soy-free chow only (control group, n = 8), or with the addition of oestradiol-3 benzoate (E2B) (10mg/kg, n = 10) or equol (400 mg/kg, n = 10). At baseline and after 6-week treatment period, proximal tibia and lumbar spine BMD were measured using computer tomography. Animals were then sacrificed, blood was collected and uteri were removed.. Similarly to E2B, dietary equol decreased weight gain and showed mild uterotropic activity. E2B attenuated ovx induced BMD loss at proximal tibia whereas equol had no effect. At lumbar spine, however, equol not only attenuated trabecular bone loss but also increased its density. This effect was also apparent in animals treated with E2B. Cortical BMD at proximal tibia and lumbar spine were not very much influenced by ovx and treatment with E2B or equol did not induce significant changes at these sites. Plasma osteocalcin and type I collagen fragments (cross-laps) in equol treated animals did not differ from the controls whereas in E2B treated animals they were both significantly decreased.. In spite of its mild uterotropic potential, dietary equol shows limited bone sparing effects in ovx rats.

Topics: Animals; Bone Density; Dietary Supplements; Equol; Estradiol; Female; Isoflavones; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Rats; Rats, Sprague-Dawley

Certain plant extracts have been the object of recent studies due to their mild estrogenic action and their possible potential role in osteoporosis prevention and/or treatment. The present study was undertaken to investigate the possible protective effect of the aqueous solution of the plant Onobrychis ebenoides, with proven in vitro mild estrogenic action, on bone mass loss of the ovariectomized (Ovx) rat experimental model of osteoporosis.. Forty intact female mature (10-month-old) Wistar rats were separated into three groups: Ovx, Ovx plus plant extract (Ph) and sham-operated (control). Ph administration in the drinking water at a dose of 300 mg/kg body weight/day commenced immediately after Ovx. Bone mineral density (BMD) values, percentage change from the baseline measurement and histomorphometry of the tibia, as well as body and uterine weight, were examined and compared between groups.. Comparison of BMD absolute values of the whole tibia of Ovx + Ph and Ovx animals at both 3 and 6 months post-Ovx were highly significant (p < 0.0005), showing a protective effect on treated animals. The extract did not appear to have such a beneficial effect on BMD of the proximal tibia of the treated animals compared to the Ovx animals after 3 months; however, a significant protective effect was observed at 6 months post-Ovx in treated animals compared to the Ovx (p = 0.015). When the % changes from baseline measurement of the whole tibia of Ovx + Ph and controls were compared, there was no significant difference at 3 or 6 months, demonstrating a highly protective effect; the respective comparisons of proximal tibia % changes did not display such protection. Body and uterine weight comparisons showed no significant difference between Ovx and treated rats, whereas, the level of significance for each group compared to controls was p < 0.0005.. The Ph studied showed a highly significant protective effect on BMD of the whole tibia of Ovx rats after 3 and 6 months of treatment, compared to the non-treated animals. Its effect on the proximal tibia was less pronounced, but also statistically significant compared to non-treated rats after 6 months. The lack of significant effect on body and uterine weight is in favor of its selective estrogen receptor modulator-like activity, and merits further studies.

Topics: Absorptiometry, Photon; Animals; Bone Density; Fabaceae; Female; Models, Animal; Osteoporosis; Phytoestrogens; Plant Extracts; Rats; Rats, Wistar; Treatment Outcome

Phystestrogens are organic compounds produced by a large variety of plants with protective function against the invasion of them by microorganisms. Phystestrogens, and among them isoflavones, have a great similarity with estradiol, principal endogenous estrogen. Those known most for their estrogenic activity are daidzeine and genisteine. Due to the existence of contradictory data on the effects of soy isoflavones on the most outstanding health disorders of menopause such as osteoporosis and hot flushes, and its ineffective role in the improvement of the lipid profile, it is recommendable to continue choosing hygienic-dietary and conventional drug treatments. However, we could introduce soy and soy derived products within a balanced, varied and adequate diet for these women.

Topics: Atherosclerosis; Bone Density; Female; Glycine max; Humans; Isoflavones; Lipids; Menopause; Osteoporosis; Phytoestrogens

Reduced estrogen levels occurring during menopause in woman are accompanied by a variety of disorders, e. g., hot flushes, depressions, osteoporosis, increase of body weight, and reduced movement drive. In this study we investigated the combined effects of physical activity, estradiol substitution, and a phytoestrogen-rich diet on bone mineral density, increase of body weight, and movement drive in an animal model. Ovariectomized (OVX) female Wistar rats were either fed an isoflavone-rich diet (IRD) or substituted with 17beta-estradiol (E2) for 3 months. Sham-operated rats (Sham) and vehicle-treated OVX animals served as controls. One half of the animals had the opportunity of voluntary wheel running. OVX rats displayed an eight times lower movement activity than Sham animals. E2 treatment, but not IRD, significantly increased the movement activity of OVX rats. During 3 months the lowest increase of body weight was observed in Sham animals, the highest rate in OVX animals. Along with running activity E2 treatment, but not IRD, also lowered the increase of body weight significantly compared to OVX animals. Bone mineral density (BMD) in the trabecular area of the tibia was strongly reduced in OVX rats compared to Sham animals. In contrast to IRD, E2 substitution resulted in a protection of BMD in this area compared to OVX animals. Our data demonstrate that body weight, movement drive, and BMD are positively influenced by E2. The steroid estrogen acts in the trabecular area of the tibia in a bone-protective manner, increases movement drive and antagonizes the increase of body weight. All these effects could not be observed in animals fed an isoflavone-rich diet.

Topics: Animals; Body Weight; Bone Density; Dietary Supplements; Disease Models, Animal; Estradiol; Female; Isoflavones; Motor Activity; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Rats; Rats, Wistar

Topics: Alzheimer Disease; Breast Neoplasms; Cardiovascular Diseases; Colorectal Neoplasms; Dehydration; Estrogen Replacement Therapy; Estrogens; Female; Hot Flashes; Humans; Menopause; Osteoporosis; Phytoestrogens; Progesterone; Urination Disorders; Vaginal Diseases

This study investigated a phytoestrogen-rich herb formula, Xianlinggubao (XLGB) (including genistein 510 microg/g and daidzein 2500 microg/g), concerning prevention of OVX-induced deterioration of musculoskeletal tissues in 11-month-old female Wistar rats, which were randomized into Sham, OVX, and XLGB groups. Daily oral administration of XLGB (250 mg/kg/day) started after OVX for 3 months. mRNA of MHC-I IIa IIb of abductor muscle was determined by RT-PCR. The proximal femoral BMD and geometry, microarchitecture, and mechanical strength were evaluated by pQCT, micro-CT, and compressive testing, respectively. The bone turnover biochemical markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) were evaluated. The results showed that (1) XLGB-treated OVX rats showed no difference compared to the Sham group, whereas OVX induced significant deterioration in variables related to bone density, microarchitecture, and mechanical strength (P < 0.05); (2) biochemical markers showed no difference between sham and XLGB groups as compared with higher bone turnover in OVX rats (P < 0.05); (3) mRNA expression of MHC-I IIa IIb was downregulated in OVX rats but upregulated after XLGB treatment (P < 0.05); and (4) as compared with the OVX group, no uterine hypertrophy was found in XLGB-treated rats. In conclusion, findings of this study suggested that the herbal preparation XLGB was able to prevent OVX-induced deterioration of musculoskeletal tissues at the hip without causing uterine stimulation.

Topics: Animals; Biomarkers; Bone Density; Female; Femur; Genistein; Growth Inhibitors; Isoflavones; Muscle, Skeletal; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; Rats, Wistar

Certain plant-derived compounds show selective estrogen receptor modulator (SERM) activity and may therefore be an alternative to the conventional hormone replacement therapy, which prevents osteoporosis but is also associated with an increased risk of breast and endometrial cancers. In the current study, we tested the effects of the hop-derived compounds 8-prenylnaringenin, 6-prenylnaringenin, xanthohumol and isoxanthohumol (1) to modulate markers of differentiation and gene expression in osteoblasts and (2) to regulate proliferation in MCF-7 breast cancer cells. Additionally, we analyzed the ER-binding affinities of these hop compounds as well as the ER-mediation of their effects. Bone-forming activity and ER-subtype specificity were investigated by measuring alkaline phosphatase (AP) activity in hFOB/ERalpha cells and regulation of gene transcription for AP, interleukin-6, pS2 and von Willebrand factor (VWF) in U-2 OS/ERalpha and U-2 OS/ERbeta cells. Our results demonstrate that AP, pS2 and VWF mRNA levels are significantly increased by the compounds in an estrogen-like manner via both ERalpha and ERbeta, while IL-6 is down-regulated in U-2 OS/ERalpha cells. Consistently, AP enzymatic activity is up-regulated by all compounds in hFOB/ERalpha9 cells. Depending on their concentration, all compounds show proliferative effects in MCF-7 cells. Except for 8-PN the hop constituents display an ERbeta-preference. Reversal of estrogen-specific AP-induction in Ishikawa cells indicates an ER-regulated mechanism. Finally, the flavonoids display cytotoxic effects only at high concentrations (> or =10(-4)M). In summary, we have demonstrated for the first time that specific phytoestrogen compounds found in hop extracts exert estrogen-like activities on bone metabolism. Regarding a potential for use in osteoporosis-prevention therapy, the dosage of a phytoestrogen, which is taken, will play an important role concerning a desired in vivo profile.

Topics: Adult; Alkaline Phosphatase; Animals; Breast Neoplasms; Cell Line; Cell Line, Tumor; Cell Proliferation; CHO Cells; Cricetinae; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Ethinyl Estradiol; Female; Humans; Humulus; Osteoblasts; Osteoporosis; Osteosarcoma; Phytoestrogens; Plant Extracts; Up-Regulation

Topics: Antioxidants; Bone Resorption; Carrier Proteins; Contraindications; Female; Hormone Replacement Therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoflavones; Leptin; Membrane Glycoproteins; Osteoporosis; Phytoestrogens; Plant Preparations; Raloxifene Hydrochloride; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Selective Estrogen Receptor Modulators; Teriparatide

To observe the effect of phytoestrogen (PE) in preventing and treating osteoporosis in ovariectomized rats.. Forty-five Wistar female rats, 3 months old, were randomly divided into the sham-operated group, the model group, low dose and high dose PE groups, and the positive control group, 9 in each group. All rats, except that those in the sham operated group were simutaneously operated, were ovariectomized. The medication started from the 31st days after operation by daily given saline per os to the sham-operated group and the model group, PE per os to the PE groups, and estradiol by intramuscular injection to the positive control group. The animals were sacrificed 90 days later, their sera were collected for determination of biochemical parameters, their right femoral bone was taken to detect the bone mineral density (BMD), left femoral bone to examine pathology of bone trabecula, and whole uterus was weighed to calculate the uterine index.. PE could increase the BMD level, serum estradiol and inorganic phosphorus content, and uterine index, lower serum BGP, tartrate-resistant acid phosphatase (TRAP), alkaline phosphatuse (AKP) and interleukin-6 levels. Pathological examination showed that in the model group, the cortex of bone thinned, bone trabecula thinned also, with poor integrity, distorted, broken and decreased in size, while in the PE groups, the above-mentioned changes were significantly alleviated.. PE is effective in preventing and treating osteoporosis in ovariectomized rats.

Topics: Alkaline Phosphatase; Animals; Bone Density; Female; Isoflavones; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Preparations; Random Allocation; Rats; Rats, Wistar

Topics: Breast Neoplasms; Female; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations; Treatment Outcome

Topics: Animals; Bone Remodeling; Estrogens, Non-Steroidal; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations

Noninvasive assessment of bone mineral density, geometrical and biomechanical properties in premenopausal women with dietary intake of phytoestrogens and comparison of these parameters with those of age-matched female subjects with "Mediterranean" dietary intake lacking in these substances.. Volumetric cortical, trabecular and total mineral density and bone geometrical properties were evaluated in 15 female subjects with phytoestrogens dietary intake. Peripheral quantitative Computed Tomography (pQCT) was used to make measurements at the distal radius of the nondominant forearm. Fifteen age-matched subjects with "Mediterranean" dietary intake were chosen as a control group. Cross-sectional area (Total A), trabecular area (TA), cortical area (CA), cortical thickness (CThk) and strength strain index (SSI) were assessed as biomechanical parameters.. Daily consumption of phytoestrogens was significatively different in the two groups (phy: 17.45 mg/die vs ctr: 0.35; p < 0.0005), while calcium intake was similar (phy: 652 mg/die vs ctr: 650). Total (0.460 g/cm3 vs ctr: 0.433) and trabecular (phy: 0.209 g/cm3 vs ctr: 0.189) bone mineral densities, such as SSI (phy: 925 mm3 vs ctr: 894) values, were higher in women with dietary intake of phytoestrogens, in comparison with the relative controls, but not significantly (p = ns). Among geometrical parameters, total area and cortical area were tendential in women with a vegetarian diet while cortical thickness was the same in both groups.. pQCT showed higher bone mineral density (total and trabecular) and SSI values in premenopausal women with dietary intake of phytoestrogens. Despite the lack of statistical significance, these preliminary results, should further support the few literature findings about the potential role of phytoestrogens consumption in preventing trabecular bone loss. However, further studies are warranted to evaluate definitively the efficacy of phytoestrogens in preventing postmenopausal osteoporosis.

Topics: Adult; Animals; Biomechanical Phenomena; Bone Density; Diet Records; Diet, Vegetarian; Eggs; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Mediterranean Region; Milk; Osteoporosis; Phytoestrogens; Plant Preparations; Plants; Premenopause; Radius; Tomography, X-Ray Computed

Dairy foods provide the major, readily absorbed sources of calcium. Women aged 40 years and over should consume 3-4 serves of low-fat dairy food per day. If calcium supplements are required, the best absorption rate is from a dose of 500-600 mg of calcium once or twice daily. Exercise, alone or in combination with other therapeutic interventions, is effective in preventing bone loss. Vitamin D supplements may be necessary for women with inadequate sun exposure. Salty foods and the addition of salt to food should be avoided. While there is emerging evidence for the role of phytoestrogens in bone health, more human trials are required to strengthen this evidence.

Topics: Adult; Calcium, Dietary; Diet; Estrogens, Non-Steroidal; Exercise; Female; Humans; Isoflavones; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations; Plants; Women's Health