Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial

Abstract

Female age-related estrogen deficiency increases the risk of osteoporosis, which can be effectively treated with the use of hormone replacement therapy. However, hormone replacement therapy is demonstrated to increase cancer risk. Bioavailable isoflavones with selective estrogen receptor affinity show potential to prevent and treat osteoporosis while minimizing or eliminating carcinogenic side effects. In this study, we sought to determine the beneficial effects of a bioavailable isoflavone and probiotic treatment against postmenopausal osteopenia. We used a novel red clover extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly promote uptake and a favorable intestinal bacterial profile to enhance isoflavone bioavailability. This was a 12-mo, double-blind, parallel design, placebo-controlled, randomized controlled trial of 78 postmenopausal osteopenic women supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25 μg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked placebo [control (CON)]. RCE significantly attenuated bone mineral density (BMD) loss at the L2-L4 lumbar spine vertebra ( < 0.05), femoral neck ( < 0.01), and trochanter ( < 0.01) compared with CON (-0.99% and -2.2%; -1.04% and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE group ( < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE significantly elevated the plasma isoflavone concentration ( < 0.05), the urinary 2-hydroxyestrone (2-OH) to 16α-hydroxyestrone (16α-OH) ratio ( < 0.05), and equol-producer status ( < 0.05) compared with CON. RCE had no significant effect on other bone turnover biomarkers. Self-reported diet and physical activity were consistent and differences were nonsignificant between groups throughout the study. RCE was well tolerated with no adverse events. Twice daily RCE intake over 1 y potently attenuated BMD loss caused by estrogen deficiency, improved bone turnover, promoted a favorable estrogen metabolite profile (2-OH:16α-OH), and stimulated equol production in postmenopausal women with osteopenia. RCE intake combined with supplementation (calcium, magnesium, and calcitriol) was more effective than supplementation alone. This trial was registered at clinicaltrials.gov as NCT02174666.

Effect of Acupoint Catgut Embedding on Intestinal Flora in Rats with Ovariectomized Osteoporosis

“…Besides, decreased estrogen can also reduce the sensitivity of bone to mechanical stimulation, resulting in pathological changes similar to disuse bone loss [11] . Studies con rm that decreased estrogen can also reduce the diversity of intestinal ora [12][13] , and Intestinal ora can affect bone metabolism by releasing small molecules, such as estrogen analogs and serotonin, to participate in immune regulation and affect the absorption and metabolism of calcium and phosphorus [14][15] . Therefore, it can be considered that the development of PMOP is associated with the diversity of intestinal ora.…”

Comparative Analysis of Bone Mechanical Properties of Adipose-Derived Mesenchymal Stem Cells and Raloxifene in Treatment of Osteoporosis

“…The bone mass is determined by the microstructure, metabolic conversion, mineralization, and bone matrix characteristics of bones. BMD is expressed in terms of bone mass per unit area or per unit volume 13) . BMD measurements of tibia in each group showed that the BMD value in group MOD was significantly lower than group CON, group AMSCs, and group RAL, indicating that osteoporosis causes bone mass lost and bone formation decline.…”

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies

“…Recently, in a randomized clinical trial, isoflavone treatment has achieved a decline in the BMD loss, together with an increased in bone turnover. Moreover, the combination of this phytoestrogens with calcium, magnesium and calcitriol showed even better results [100]. However, its effectiveness remains controversial since a meta-analysis of 10 long term clinical trials concluded that soy isoflavones did not show significant improvement in lumbar spine, total hip or femoral neck BMD of postmenopausal women [101].…”