The role of botanicals in preventing bone loss in the postmenopausal state

Postmenopausal estrogen depletion is a major contributing factor to osteoporosis in women. Current osteoporosis treatments, including hormone replacement therapy and bisphosphonates, have been challenged for their risks; therefore, there has been interest in soy isoflavones and other polyphenolic-containing substances for their potential to reduce bone loss. Many polyphenols behave as estrogens in the body, restoring some of the beneficial actions of estrogen to bone. The ability of soy isoflavones to reduce bone loss associated with estrogen deficiency is hypothesized to be dependent on isoflavone composition, dose, and equol-producing ability. The aim of this research was to determine whether equol-producing ability of an individual affects bone resorption when given soy interventions of genistein-rich or mixed isoflavone supplements of varying doses. This study was a blinded, partially-randomized, crossover intervention trial in which postmenopausal women (n=24) were prescreened for their ability to convert daidzein to equol (n=8 equol-producers). The subjects received 5 soy isoflavone extract interventions, including two doses of a genistein-rich soy supplement and three doses of mixed isoflavones in various proportions, as well as a bisphosphonate (risedronate) positive control. Subjects were intravenously dosed with 41Ca to deep label their skeletons so that urinary excretion of 41Ca could be measured to assess bone resorption, calculated as relative resorption (RR). There was no difference between equol-producers and non-producers, and the commercially available Novasoy® had the greatest antiresorptive effect of the soy interventions with RR=0.924 (p\u3c0.0001) compared to risedronate (RR=0.847, p=0.0009). The radio-isotope, 45Ca, was used as a proxy to the 41Ca methodology in human subjects to investigate the effect of supplementation of high and low doses of blueberry, plum, grape, grape seed extract, and resveratrol, as well as two forms of soy isoflavones as a crossover design in ovariectomized rats (n=16 rats for each extract intervention). Bone resorption was assessed by urinary excretion of 45Ca/Ca ratio during an intervention period compared to a washout period. A high dose of grape seed extract, and both doses of blueberry and plum were able to reduce bone resorption with relative resorption ranging from 0.66 to 0.84. There was a non-significant dose-response in grape seed extract and a significant dose-response in plum (p=0.02)