The potential effects of isoflavones on nuclear receptor modulation in bone remodeling: A review (original) (raw)
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Molecules, 2020
Receptor activator of nuclear factor-κB ligand (RANKL) is a cytokine responsible for bone resorption. It binds its receptor RANK, which activates osteoporosis. High levels of osteoprotegerin (OPG) competitively binding RANKL limit formation of ligand-receptor complexes and enable bone mass maintenance. The new approach to prevent osteoporosis is searching for therapeutics that can bind RANKL and support OPG function. The aim of the study was to verify the hypothesis that isoflavones can form complexes with RANKL limiting binding of the cytokine to its receptor. Interactions of five isoflavones with RANKL were investigated by isothermal titration calorimetry (ITC), by in silico docking simulation and on Saos-2 cells. Daidzein and biochanin A showed the highest affinity for RANKL. Among studied isoflavones coumestrol, formononetin and biochanin A showed the highest potential for Saos-2 mineralization and were able to regulate the expression of RANKL and OPG at the mRNA levels, as well...
The effects of estrogen depletion and isoflavones on bone metabolism in rats
Nutrition Research, 2003
To examine a potential role for phytoestrogens in postmenopasual bone loss, the ovariectomized (OVX) rat model has been used to investigate whether lower than previously used doses of isoflavones are beneficial in impeding ovarian hormone deficiency-associated bone loss. In this study, thirty-two 90-day-old Sprague-Dawley rats were randomly divided into four groups and fed a semi-purified diet with or without isoflavones for forty days. The treatment groups were sham-operated (sham), OVX, OVXϩ isoflavones (0.575 mg/g of dietary protein), and OVXϩ isoflavones (1.15 mg/g of dietary protein). Ovariectomy reduced (P Ͻ 0.05) 4 th lumbar vertebral, tibial, and femoral bone density, and femoral bone strength; increased (P Ͻ 0.05) urinary excretion of Ca; and did not affect serum Ca and Mg, blood ionized Ca, or urinary Mg excretion when compared with the sham group. We concluded that dietary supplementation of isoflavones at the two doses given had no effect on bone quality or other parameters of bone metabolism.
The Journal of …, 2001
We assessed the dose-dependent effects of daily soybean isoflavone (IF) consumption in reversing bone loss in adult ovariectomized rats. On d 0, female Wistar rats (7 mo old; n ϭ 55) were either sham-operated (SH; n ϭ 14) or ovariectomized (n ϭ 41). On d 80, intermediate rats (SH: n ϭ 5; ovariectomized: n ϭ 5) were killed to confirm the ovariectomy-induced bone loss. The remaining ovariectomized rats were randomly assigned to one of four groups of nine rats each and fed soybean IF (mixed with a soy protein-free semipurified diet) at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) mg/(kg body ⅐ d) for 84 d. Simultaneously, SH rats were fed the semipurified diet without any additional compound and killed on d 164, as were the other rats. As expected, both bone mineral density in the total femur and in its diaphyseal and metaphyseal subregions and cancellous bone area/measured surface in the distal femur metaphysis were lower in OVX than in SH rats (P Ͻ 0.05). OVX rats had higher plasma osteocalcin concentration and urinary deoxypyridinoline excretion than SH rats (P Ͻ 0.05). On d 164, osteocalcin and deoxypyridinoline concentrations were lower in IF40 or IF80 rats than in OVX rats (P Ͻ 0.05). Nevertheless, neither bone mineral density nor cancellous bone area was greater in IF-fed rats than in OVX rats. Therefore, in adult ovariectomized rats, daily soybean IF consumption decreased bone turnover but did not reverse established osteopenia. J. Nutr. 131: 723-728, 2001.
Although hormone replacement therapy (HRT) and calcium (Ca) supplementation preserve bone mass more when combined, there is a growing concern over the safety of HRT that necessitates thorough investigation of effective, alternative treatments for bone loss. While plant-derived estrogen-like compounds such as isoflavones preserve bone, it is not known whether isoflavones and Ca supplementation attenuate losses in bone mass and strength to a greater extent when combined. This study compared the effects of an isoflavone extract ϩ high Ca to isoflavone extract or high Ca alone on preservation of bone mineral density (BMD) and biomechanical strength in ovariectomized (ovx) rats. Rats were sham-operated (n ϭ 10) or ovx (n ϭ 40). Shams were fed a 0.2% Ca diet. Ovx rats were randomized to a 0.2% Ca diet alone (OVX) or with isoflavone extract (IE; 1.6 g/kg diet) or to a high Ca diet (Ca; 2.5%) alone or a high Ca diet with the isoflavone extract (IE ϩ Ca) for 8 weeks. BMD of femur and lumbar spine were measured by dual-energy X-ray absorptiometry. The biomechanical strength of femurs and individual vertebra was measured by three-point bending and compression testing, respectively. The average food intake was lowest (P Ͻ 0.05) among sham and IE groups and greatest (P Ͻ 0.05) among the OVX group. Final body weight was lowest (P Ͻ 0.05) among shams and highest (P Ͻ 0.05) among the OVX group while IE ϩ Ca were lighter (P Ͻ 0.05) than all ovx groups. Femur and vertebra BMD was greater (P Ͻ 0.05) among IE ϩ Ca and sham rats compared to IE, Ca, or OVX rats. Although there were differences in femur BMD among groups, biomechanical properties at the femur midpoint did not differ among groups, possibly due to the lack of cortical bone loss at this site. Conversely, vertebra biomechanical strength was greater (P Ͻ 0.05) among IE ϩ Ca and Ca alone groups compared to IE alone. Uterine weight was higher (P Ͻ 0.05) among shams than OVX and IE with no difference among shams, Ca, or IE ϩ Ca rats, suggesting that the isoflavones did not have an uterotrophic effect. In conclusion, isoflavones combined with high Ca are more protective against the loss of femur and vertebra BMD than isoflavones or high Ca diet alone.
Journal of Functional Foods, 2014
In a longitudinally designed study, we tested whether an isoflavone enriched soy extract (SE) stimulated peak bone gain in rats during growth and maturity so as to confer better bone conserving effect after ovariectomy with concurrent treatment discontinuation. Weaned female rats were given SE or vehicle for 12-weeks and bone parameters were recorded (baseline). One group was then ovariectomized (OVx) and the other group sham operated. Vehicle group after OVx was given 17b-estradiol (E2) or continued with vehicle (OVx + vehicle). SE group after OVx was given vehicle (SEV). After 12-weeks, all groups were killed (endpoint). At baseline, SE group had greater cortical bone parameters over control. At endpoint, SEV group displayed significant bone conservation which was comparable to OVx + E2 group. Data suggest that SE enhanced peak bone accrual that supported skeletal preservation post-OVx on a par with E2 supplementation, not withstanding SE withdrawal at OVx.
Effects of herbal preparations containing isoflavones on bone metabolism in postmenopausal women
Journal of Food and Drug Analysis, 2020
The effects of the mixed herbal preparation "Tzuo-Kuai-Wuan" (TKW) on bone metabolism were compared with a single herb containing equivalent amounts of isoflavones, daidzein and genistein, and a combined estrogen-progesterone therapy (EPT). One hundred women completed the trial, 33 in group A, consuming a single herb, 30 in group B, consuming TKW, and 37 in group c, receiving EPT. In both herbal groups, the serum levels of daidzein significantly increased after treatment for 6 months (224% in group A and 234% in group B, both p < 0.01), though the serum levels of genistein did not change significantly. In group c, serum levels of either isoflavone changed only slightly. After 6 months of treatment, the bone formation marker (bone specific alkaline phosphatase [BSAP]) significantly increased in group B, but not in group A (25.4% vs. 15.9%, p < 0.01 and p = 0.09, respectively). The elevation of BSAP was related to increased serum daidzein and genistein (ß = 0.498 and 0.248, p < 0.01 and p = 0.03, respectively). The bone resorption marker (urinary deoxypyridinolines/creatinine [Dpd/cr]) was nearly the same at beginning of the study and after treatment in both herbal groups. In contrast, BSAP and Dpd/cr significantly decreased after 3 and 6 months of treatment in group c (BSAP: 10.4% and 30.3%; Dpd/cr: 21.7% and 43.8%, all p < 0.01 in paired t-tests). Thus, we conclude that TKW stimulates bone formation, in contrast to EPT which primarily inhibits resorption. This effect appears to be related to the amount of isoflavones. Further, the stronger effect in women consuming TKW than consuming a single herb that contains equivalent amounts of isoflavones suggests higher synergistic or additive effect of other components than isoflavones in TKW.
Soy isoflavones for osteoporosis: An evidence-based approach
Maturitas, 2011
Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.