Background:No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women. Objective: Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones (80.4 mg/d) in attenuating bone loss during the menopausal transition. Design: Perimenopausal subjects were randomly assigned, double blind, to treatment: isoflavone-rich soy (SPI+; n = 24), isoflavone-poor soy (SPIϪ; n = 24), or whey (control; n = 21) protein. At baseline and posttreatment, lumbar spine bone mineral density (BMD) and bone mineral content (BMC) were measured by using dual-energy X-ray absorptiometry. At baseline, midtreatment, and posttreatment, urinary N-telopeptides and serum bonespecific alkaline phosphatase (BAP) were measured. Results: The percentage change in lumbar spine BMD and BMC, respectively, did not differ from zero in the SPI+ or SPIϪ groups, but loss occurred in the control group (Ϫ1.28%, P = 0.0041; Ϫ1.73%, P = 0.0037). By regression analysis, SPI+ treatment had a positive effect on change in BMD (5.6%; P = 0.023) and BMC (10.1%; P = 0.0032). Baseline BMD and BMC (P ≤ 0.0001) negatively affected the percentage change in their respective models; baseline body weight (P = 0.0036) and bone-free lean weight (P = 0.016) contributed positively to percentage change in BMD and BMC, respectively. Serum BAP posttreatment was negatively related to percentage change in BMD (P = 0.0016) and BMC (P = 0.019). Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones, not soy protein, exerted the effect. Conclusion: Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women.Am J Clin Nutr 2000; 72:844-52. KEY WORDSSoy, isoflavones, bone density, lumbar vertebrae, biochemical markers, menopause, bone mineral content, perimenopausal women INTRODUCTIONCurrent therapies for treating osteoporosis include estrogen and hormone replacement therapies (ERT and HRT), bisphosphonates, calcitonin, and raloxifene. Because of possible contraindications of ERT and HRT, such as breast cancer, endometrial adenocarcinoma, and undesirable side effects (1), compliance with hormonal therapy is poor (2), leading to loss of treatment efficacy (3). Continued uterine bleeding and other adverse side effects of HRT cause women to search for alternatives to traditional therapy. Isoflavone-containing soy may be a potential alternative for preventing bone loss during the menopausal transition.Isoflavones, found predominantly in soy products, are estrogen-like substances structurally and functionally similar to 17 ␤-estradiol (4). On the basis of evidence primarily from animal and in vitro studies, isoflavones are thought to exert both estrogenic and antiestrogenic effects, depending on the tissue in which they act (5). Isoflavones may exert a weak antagonistic effect on the estrogen receptor (5), thereby having an antiestrogenic effect on uterine and breast tissue (6), where excess estrogen ...

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical anti-oxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation. Future research is needed to determine which of the flavonoids and their metabolites are most effective and at what dose, as well as the mechanism of modulating cellular events, in order to set priorities for clinical trials.

Our results do not show a bone-sparing effect of extracted soy isoflavones, except for a modest effect at the femoral neck. This trial was registered at clinicaltrials.gov as NCT00043745.

In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms.