phytoestrogens and Bone-Diseases--Metabolic

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

Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life. The phytoestrogen genistein at a dose of 54 mg daily in osteopenic postmenopausal women after 2 years implies an improvement on quality of life and depression symptoms.. Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on quality of life parameters. However, because of known or suspected serious side effects of conventional hormone therapy, there is a need for alternatives.. We conducted a double-blind randomized placebo-controlled trial using the isoflavone genistein, 54 mg, or placebo for 2 years. In this trial, we recruited 262 postmenopausal women aged 49 to 67 years.. At baseline, after 1 year, and at final visit, participants filled in the Short Form of 36 questions (SF-36) and the Zung Self-rating Depression Scale (ZSDS). For the placebo group, scores on all dimensions of the SF-36 decreased after 1 and 2 years. The genistein group showed increases on all dimensions of the SF-36 at the end of the study. There were, however, statistically significant differences in changes of scores between the two intervention groups. For the ZSDS, similarly, significant differences were found between groups.. In conclusion, the findings of this randomized trial showed that genistein improves quality of life (health status, life satisfaction, and depression) in osteopenic postmenopausal women.

Topics: Aged; Bone Density; Bone Diseases, Metabolic; Depression; Double-Blind Method; Estrogen Replacement Therapy; Female; Femur Neck; Genistein; Humans; Lumbar Vertebrae; Middle Aged; Phytoestrogens; Postmenopause; Psychiatric Status Rating Scales; Psychometrics; Quality of Life

Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.. We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.. The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year.. Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses.. Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers.. After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups.. After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.

Topics: Aged; Biomarkers; Bone Density; Bone Diseases, Metabolic; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Double-Blind Method; Endometrium; Female; Genistein; Humans; Mammography; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; RNA, Messenger; Sister Chromatid Exchange

Genistein is an isoflavone phytoestrogen derived from the soybean which acts as natural selective estrogen receptor modulator. Various studies have pointed out its cardioprotective role. The aim of the study was to evaluate the haemostatic effects of genistein in postmenopausal women.. In this double-blind placebo-controlled trial we enrolled 104 healthy postmenopausal women with osteopenia. 53 patients (mean age 54.9+/-4.2 yr; BMI 23.4+/-3.2 Kg/m(2)) received genistein (54 mg/day) and 51 patients (mean age 55.4+/-4.3 yr; BMI 23.6+/-3.6 Kg/m(2)) received an identical placebo-tablet. Both groups received a calcium and vitamin D supplement. Plasma levels of D-dimer (DD), plasminogen activator inhibitor-1 (PAI-1) and prothrombin fragment 1+2 (F1+2) were measured at baseline and after 6 and 12 months of treatment.. Baseline characteristics of the two groups were similar. Compared with placebo, genistein decreased significantly DD (p<0.001), but did not affect PAI-1 and F 1+2 plasma levels.. The results of our study do not confirm effects of genistein on activation of the haemostatic system, but on the contrary the significant decrease of DD could indicate a possible cardioprotective role of genistein in postmenopausal women.

Topics: Bone Diseases, Metabolic; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Genistein; Hemostasis; Humans; Middle Aged; Outpatients; Peptide Fragments; Phytoestrogens; Plasminogen Activator Inhibitor 1; Postmenopause; Prothrombin; Treatment Outcome

The current strategies to prevent and treat menopausal osteoporosis are hormone replacement therapy (HRT). However, the long-term use of hormone replacement therapy is limited due to its side-effects. Alternately, use of phytoestrogens has been implicated. Trigonella foenum graecum (TFG) seeds are rich in phytoestrogen and known traditional medicine to treat menopause induced hyperlipidemia. Therefore, in this study, we evaluated the role of dietary TFG seed extract on bone structure and mechanical properties in ovariectomized rats.. Twenty four female Wistar rats were randomly allocated into four groups; 1) control, 2) ovariectomized, 3) ovariectomized + TFG seed extract and 4) ovariectomized + 17β-estradiol. TFG seed extract/17β-estradiol was administered for 30 days, 14 days after ovariectomy. After the treatment, right femora were collected to measure the length and biomechanical properties, and left femora were gathered to study the micro architectural changes while tibia were collected to measure the dry weight.. Maximum flexor load to break femur bone was significantly low in ovariectomized rats in comparison with control rats (P<0.05). Supplementation with TFG significantly improved the maximum flexor load (P<0.05) and tibia dry weight (P<0.01) compared to ovariectomized untreated rats. TFG administration also significantly preserved the trabecular (P<0.01) and cortical bone (P<0.05) thickness compared to ovariectomized rats.. This study found that dietary intake of TFG seeds can improve the bone structure and biomechanical properties in ovariectomized rats indicating that TFG may be an alternative treatment strategy to prevent the menopause induced osteopenia.

Topics: Animals; Bone and Bones; Bone Diseases, Metabolic; Female; Menopause; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats, Wistar; Seeds; Trigonella

Hormone replacement therapy has been used as an effective treatment for the prevention of bone loss in postmenopausal women. In our previous study, QiBaoMeiRan formula (QBMR) had estrogenic activity and could relieve symptoms of hot flushes and body weight increase induced by estrogen decline. However, no evidence base links QBMR to preventing bone loss. The aim of this study is to investigate the effect of QBMR on bone loss.. The ovariectomized rat model was established, and ovariectomized rats were treated with QBMR at doses of 0.875, 1.75, and 3.5 g/kg per day for 8 weeks. Biochemical parameters, bone mineral density, structural morphometric traits and histological characteristics of trabecular bone were assessed.. QBMR treatment significantly decreased the increase in serum alkaline phosphatase, bone Gla-protein and C-telopeptide fragments of type I collagen and decreased the decline of serum calcium and phosphorus in the circulation of ovariectomized rats. QBMR completely corrected the decrease in bone mineral density in lumbar vertebrae (L4-L6) comparable to the sham group. In addition, QBMR treatment also significantly ameliorated the decrease of structural parameters of femur trabecular bone, bone volume fraction, trabecular number, trabecular thickness and bone mineral density as well as the increase in trabecular separation by micro-computerized tomography scanning. These were also confirmed by bone histological results that showed its protective action.. Our results indicated that QBMR had a definite anti-bone loss effect and will have potential to be used for the treatment of postmenopausal osteoporosis.

Topics: Alkaline Phosphatase; Animals; Bone Density; Bone Diseases, Metabolic; Calcium; Collagen Type I; Disease Models, Animal; Drugs, Chinese Herbal; Female; Femur; Lumbar Vertebrae; Ovariectomy; Peptides; Phosphorus; Phytoestrogens; Rats; Rats, Sprague-Dawley

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

Topics: Animals; Bone Diseases, Metabolic; Female; Isoflavones; Ovariectomy; Phytoestrogens

Topics: Animals; Bone Diseases, Metabolic; Female; Isoflavones; Ovariectomy; Phytoestrogens

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

Formononetin (Formo) prevents ovariectomy (Ovx)-induced bone loss in rats. However, there are no reports on the curative effects of Formo. The objective of this study was to investigate the ability of Formo in restoring trabecular microarchitecture and promoting new bone formation in osteopenic rats.. Adult Sprague-Dawley rats were ovariectomized and left for 90 days for osteopenia to develop. After 90 days, Formo (10.0 mg kg d) was given orally for the next 12 weeks to Ovx rats in a therapeutic protocol. Sham-operated, Ovx + vehicle, and Ovx + parathyroid hormone (PTH) groups served as controls. Trabecular microarchitecture, osteoid formation, bone turnover/resorption markers, and bone osteoprotegerin-to-receptor activator for nuclear κB ligand ratio were studied. One-way analysis of variance was used to test significance of effects.. Formo treatment significantly restored the lost trabecular microarchitecture in the femurs and tibia of osteopenic Ovx rats and promoted new bone formation. Formo was devoid of any uterine estrogenicity. Serum levels of type I collagen N-terminal propeptide, which is a reliable marker of bone formation, were increased in Ovx rats treated with Formo compared with Ovx + vehicle group, and the levels were comparable with those in the sham group. Formo prevented the Ovx-induced increase in bone turnover markers, including serum osteocalcin and urinary type I collagen degradation product. Furthermore, Formo-treated Ovx rats had an increased bone osteoprotegerin-to-receptor activator for nuclear κB ligand ratio compared with the Ovx + vehicle group.. Daily oral administration of Formo for 12 weeks has a substantial anabolic effect, thus raising the possibility of its use in postmenopausal osteoporosis.

Topics: Animals; Bone Diseases, Metabolic; Bone Remodeling; Female; Femur; Isoflavones; Osteogenesis; Osteoprotegerin; Ovariectomy; Peptide Fragments; Phytoestrogens; Procollagen; RANK Ligand; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tibia

Topics: Animals; Bone Diseases, Metabolic; Female; Isoflavones; Ovariectomy; Phytoestrogens

Phytoestrogens might be an alternative medication in prophylaxis and treatment of osteoporosis. In this study, the osteoprotective effects of genistein (GEN) and equol (EQO) were evaluated. After ovariectomy, 44 rats received soy-free food (Control, C) and developed substantial osteoporosis over the course of two months. After that period, the rats were divided into different groups and fed estradiol (E), GEN or EQO for 35 days. To analyze the osteoprotective effects of the tested substances, bone biomechanical properties and histomorphometric changes of the lumbar vertebrae were evaluated. In analyzing the vertebral body compression strength, we found that the EQO (103.8%) and GEN (96.8%) groups reached similar levels relative to the E group, while the C group reached 77.7% of the biomechanical properties of the E group. EQO was significantly superior to C. The histomorphometric evaluation demonstrated an increased number of nodes in EQO- and E-treated rats compared to GEN- and C-treated rats. E led to an improvement of cortical as well as trabecular bone, an advantage that was only partly seen in the other groups. Treatment with phytoestrogens induced improved bone quality. EQO and GEN might be alternatives for hormone replacement therapy, although further studies are needed to elucidate possible side effects.

Topics: Animals; Biomechanical Phenomena; Bone and Bones; Bone Diseases, Metabolic; Compressive Strength; Equol; Estradiol; Female; Genistein; Isoflavones; Osteocalcin; Ovariectomy; Phytoestrogens; Rats

The putative skeletal effects of dietary soy phytoestrogens (SPE) were examined in comparison with those of conjugated equine estrogens (CEE; Premarin) in a 3-yr longitudinal study in ovariectomized female monkeys. Controls received alcohol-extracted soy protein with low phytoestrogen content, and treatment groups received either CEE (admixed into the control diet) or unextracted soy protein isolate containing SPE. The acknowledged bone protective effect of CEE was reflected by higher bone mass (by dual energy x-ray absorptiometry) and lower bone turnover marker levels. In contrast, control and SPE groups lost significant lumbar spine bone mineral content and density and whole body bone mineral content within the first year, resulting in reduced bone mass for both groups compared with CEE (P < 0.0005). No effect of SPE was observed for any bone mass measure (P > 0.44), although transient, estrogen-like effects of SPE on serum alkaline phosphatase, calcium, and C-terminal cross-link of type I collagen were observed at 3 months (P < 0.02). These results suggest that SPE may be poor substitutes for mammalian estrogens in protecting against bone loss resulting from estrogen deficiency.

Topics: Animals; Biomarkers; Body Weight; Bone and Bones; Bone Diseases, Metabolic; Densitometry; Diet; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Macaca fascicularis; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations