Kathy B. Hanson

The Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: a 3-y randomized controlled trial in postmenopausal women

BACKGROUND Our previous study indicated that soy protein with isoflavones lessened lumbar spine bone loss in midlife women. OBJECTIVE We examined the efficacy of isoflavones (extracted from soy protein) on bone mineral density (BMD) in nonosteoporotic postmenopausal women. We hypothesized that isoflavone tablets would spare BMD, with biological (age, body weight, serum 25-hydroxyvitamin D) and lifestyle (physical activity, dietary intake) factors modulating BMD loss. DESIGN Our double-blind, randomized controlled trial (36 mo) included healthy postmenopausal women (aged 45.8-65.0 y) with intent-to-treat (n = 224) and compliant (n = 208) analyses. Treatment groups consisted of a placebo control group and 2 soy isoflavone groups (80 compared with 120 mg/d); women received 500 mg calcium and 600 IU vitamin D(3). Outcomes included lumbar spine, total proximal femur, femoral neck, and whole-body BMD. RESULTS Analysis of variance for intent-to-treat and compliant (> or =80%) models, respectively, showed no treatment effect for spine (P = 0.46, P = 0.21), femur (P = 0.86, P = 0.46), neck (P = 0.17, P = 0.14), or whole-body (P = 0.86, P = 0.78) BMD. From baseline to 36 mo, BMD declined regardless of treatment. In intent-to-treat and compliant models, respectively, BMD decreases were as follows: spine (-2.08%, -1.99%), femur (-1.43%, -1.38%), neck (-2.56%, -2.51%), and whole body (-1.66%, -1.62%). Regression analysis (compliant model) indicated that age, whole-body fat mass, and bone resorption were common predictors of BMD change. After adjustment for these factors, 120 mg (compared with placebo) was protective (P = 0.024) for neck BMD. We observed no treatment effect on adverse events, endometrial thickness, or bone markers. CONCLUSION 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.

Isoflavone-rich soy protein prevents loss of hip lean mass but does not prevent the shift in regional fat distribution in perimenopausal women.

ObjectiveMenopause-induced estrogen deficiency increases the risk of cardiovascular disease, which is related to a shift in regional fat distribution. We tested the hypothesis that estrogen-like isoflavones in soy protein isolate (SPI+) would lessen both regional fat gain and lean loss compared with isoflavone-poor soy (SPI−). DesignPerimenopausal participants (N = 69) were randomly assigned (double-blind) to 24 weeks of treatment (40 g soy or whey protein per day): SPI+ (n = 24), SPI− (n = 24), or whey control (n = 21); each participant had blood drawn in the fasted (12 hours) state, had physical activity assessed, and kept a 5-day food diary. Dual-energy x-ray absorptiometry was used to examine the effects of SPI+ on regional fat and lean tissue distribution changes in the waist, hip, and thigh regions. ResultsMean body mass increased (P < 0.01) in each group, but treatment had no effect on gain in overall body mass, fat mass, or lean mass using analysis of variance. In all treatment groups combined, lean mass increased in each region; fat mass increased only in the waist region. Treatment had an effect (P = 0.039) on hip lean mass and a marginal effect (P = 0.077) on thigh fat. Regression analyses revealed that SPI+ diminished the increase in thigh fat (P = 0.018) and heightened the increase in hip lean (P = 0.035) mass. Carbohydrate intake (P = 0.006) and cohort (reflective of season; P = 0.011) contributed to the gain in thigh fat. Total protein intake (P = 0.0012), plasma insulin (P = 0.0034), and physical activity (P = 0.047) contributed to the gain in hip lean mass. ConclusionsGain in hip lean mass was greater (P = 0.014) in SPI+ than other groups, but SPI+ did not reduce the disease-promoting menopausal shift in regional fat mass.

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased.

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1 beta, IL-6, tumor necrosis factor-alpha [TNF-alpha], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-alpha, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1-6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.

Centrally located body fat is related to appetitive hormones in healthy postmenopausal women

OBJECTIVE Body composition and energy homeostasis are thought to affect the appetitive hormones: adiponectin, leptin, insulin, and ghrelin. This study examined whether centrally located fat and/or overall adiposity were related to these appetitive hormones in healthy postmenopausal women. DESIGN Overall and regional body composition was assessed by dual-energy X ray absorptiometry in relation to plasma adiponectin, serum leptin, serum insulin, and plasma ghrelin in 242 postmenopausal women. RESULTS Regression analyses revealed that the androidal-to-gynoidal fat mass ratio (18.0%), age (3.2%), and white blood cell count (1.8%) accounted for 28% of the variability in adiponectin (F=22.2; P<0.0001); androidal (waist+hip) fat mass (66.0%), androidal fat mass(2) (6.2%), whole-body lean mass (2.2%), and age (0.8%) accounted for 69% of the variability in leptin (F=102.5; P<0.0001). Regression analyses revealed that sagittal abdominal diameter (8.4%), glucose (5.4%), white blood cell count (2.6%), and dietary omega-3 fatty acids (2.0%) accounted for 32% of the variability in insulin (F=20.8; P<0.0001); waist circumference (12.7%), hip lean mass (2.0%), and white blood cell count (1.9%) accounted for 26% of the variability in ghrelin (F=20.7; P<0.0001). Our results indicated that centralized fat mass was the primary contributor to these appetitive hormones in healthy postmenopausal women. CONCLUSION Since central adiposity in postmenopausal women was related to appetitive hormones, minimizing weight gain during the menopausal transition may optimize appetitive hormones, thereby facilitating appetite control and weight maintenance.