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.

Androidal fat dominates in predicting cardiometabolic risk in postmenopausal women.

We hypothesized that soy isoflavones would attenuate the anticipated increase in androidal fat mass in postmenopausal women during the 36-month treatment, and thereby favorably modify the circulating cardiometabolic risk factors: triacylglycerol, LDL-C, HDL-C, glucose, insulin, uric acid, C-reactive protein, fibrinogen, and homocysteine. We collected data on 224 healthy postmenopausal women at risk for osteoporosis (45.8-65 y, median BMI 24.5) who consumed placebo or soy isoflavones (80 or 120 mg/d) for 36 months and used longitudinal analysis to examine the contribution of isoflavone treatment, androidal fat mass, other biologic factors, and dietary quality to cardiometabolic outcomes. Except for homocysteine, each cardiometabolic outcome model was significant (overall P-values from ≤.0001 to .0028). Androidal fat mass was typically the strongest covariate in each model. Isoflavone treatment did not influence any of the outcomes. Thus, androidal fat mass, but not isoflavonetreatment, is likely to alter the cardiometabolic profile in healthy postmenopausal women.

Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors.

Soy protein favorably alters serum lipids and lipoproteins in hypercholesterolemic individuals, thereby reducing cardiovascular disease risk. The primary purpose was to determine the effect of soy protein (40 g/d) on circulating lipids and lipoproteins or coagulation and fibrinolytic factors in normocholesterolemic and mildly hypercholesterolemic perimenopausal women. We also determined the contribution of coagulation and fibrinolytic and other factors (e.g., body size and composition; serum estrogens, ferritin, iron; dietary intake) to lipid profiles. Subjects were randomly assigned to treatment: isoflavone-rich soy (n = 24), isoflavone-poor soy (n = 24), or whey control (n = 21) protein. We measured circulating lipids and lipoproteins at baseline, wk 12 and wk 24, and coagulation/fibrinolytic factors at baseline and wk 24. Coagulation and fibrinolytic factors were not adversely affected by treatment. Treatment did not alter lipid profiles in mildly hypercholesterolemic (n = 30) or in all subjects combined. Time significantly (P < 0.001) affected serum total cholesterol, triacylglycerol, LDL cholesterol and HDL cholesterol concentrations. We could not attribute changes over time to various factors, but at baseline accounted for 57% of the variability in HDL cholesterol (P < or = 0.0001) and for 50% in the total to HDL cholesterol ratio (P < or = 0.0001). Dietary vitamin E and % energy from fat had positive effects, whereas plasma plasminogen activator inhibitor-1, fibrinogen, body weight and serum ferritin had negative effects on HDL and total to HDL cholesterol. Isoflavone-rich or isoflavone-poor soy protein had no effect on lipid profiles or coagulation and fibrinolytic factors, whereas the effect of time suggested that the hormonal milieu during the menopausal transition may have overridden any detectable treatment effect on lipids. The relationship between coagulation factors and serum lipids should be examined further as indices of cardiovascular disease risk in midlife women.

Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment.

OBJECTIVE: We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich (80.4 mg/day) and isoflavone-poor (4.4 mg/day) soy protein isolate treatment in perimenopausal women. DESIGN: In this double-blind 24-week study, 69 women were randomized to treatment: isoflavone-rich soy protein (n = 24), isoflavone-poor soy protein (n = 24), or whey protein control (n = 21). A Menopausal Index was used to assess change in hot flushes and night sweats, as well as other symptoms, at baseline, week 12, and week 24. RESULTS: Repeated measures analysis of variance indicated no treatment effect on change in hot flush (p = 0.18) and night sweat (p = 0.92) frequency, whereas there was a significant decline in hot flush (p = 0.0003) and night sweat (p = 0.0007) frequency with time in all treatment groups. Chi2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point, as well as no treatment effect on frequency or severity of other vasomotor symptoms. At the completion of the study, we found no treatment effect on retrospective perception of frequency, duration, or severity of hot flushes or night sweats. Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms, this indicated either a placebo effect or simply an improvement in symptoms during the study. CONCLUSION: In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms.

Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women.

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 (SPI-; 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 bone-specific 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 SPI- groups, but loss occurred in the control group (-1.28%, P: = 0.0041; -1.73%, 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: < or = 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.

Lifestyle and biologic contributors to proximal femur bone mineral density and hip axis length in two distinct ethnic groups of premenopausal women.

Although relatively little is known about osteoporotic risk factors in women from the Indian subcontinent, osteoporotic fractures usually occur 10-20 years earlier in Indian men and women compared with their western Caucasian counterparts. The primary purpose of this cross-sectional study was to determine the relative contributions of ethnicity, reproductive history, body size (height, weight) and composition, bone turnover, serum 25(OH)vitamin D(3) [25(OH)D(3)], dietary intake (of calcium, fiber and alcohol) and energy expenditure to femoral bone mineral density (BMD) in Indian and Pakistani (Indian/Pakistani; n = 47) versus American (n = 47) Caucasians. We also contrasted femoral BMD and hip axis length in these two distinct groups of premenopausal females living in the USA. The Indian/Pakistani (0.875 +/- 0.096) women had lower (p = 0.0014) femoral BMD (g/cm(2)) than their American (0.937 +/- 0.088) counterparts, placing them at greater osteoporotic risk. However, the shorter (p = 0.0002) hip axis length (cm) of the Indian/Pakistani (10.54 +/- 0.57) versus American (11.11 +/- 0.78) Caucasians might attenuate hip fracture risk in the former group. Significant contributors to proximal femur BMD were maximum non-pregnant lifetime weight, age at menarche, ratio of summation sigma central-to-peripheral skinfold thicknesses, calcium intake from milk and usual alcohol intake. Although serum 25(OH)D(3) and urinary N-telopeptide concentrations did not contribute to femoral BMD in the regression models, the lower (p<0.0001) serum 25(OH)D(3) (33.1 +/- 16.5 vs 64.0 +/- 22.0 nmol/l) and higher (p = 0.0004) urinary N-telopeptide (45.9 +/- 43.3 vs 18.9 +/- 18.7 nmol BCE/mmol) values in Indian/Pakistani versus American Caucasians, respectively, coupled with their lower BMD, places the Indian/Pakistani women at greater osteoporotic risk. These results suggest that a clinical trial to increase BMD and reduce osteoporotic risk is warranted in this ethnic group of premenopausal women.

Cardiovascular disease risk factors in 2 distinct ethnic groups: Indian and Pakistani compared with American premenopausal women.

BACKGROUND: Although people from the Indian subcontinent have high rates of cardiovascular disease (CVD), studies of such in Indian and Pakistani women living in the United States are lacking. OBJECTIVE: This study accounted for variability in serum lipid (total cholesterol and triacylglycerol) and lipoprotein [LDL cholesterol, lipoprotein(a), and HDL cholesterol] concentrations in Indian and Pakistani compared with American premenopausal women in the United States. Body composition, regional fat distribution, dietary intake, and energy expenditure were compared between groups. DESIGN: The 2 groups were 47 Indian and Pakistani and 47 American women. Health was assessed via medical history, physical activity, body composition (via anthropometry and dual-energy X-ray absorptiometry), dietary intake (via 7-d food records), and serum lipids. RESULTS: Serum total cholesterol, triacylglycerol, LDL cholesterol, lipoprotein(a), the ratio of total to HDL cholesterol, and the ratio of LDL to HDL cholesterol were greater (P <0.03), whereas HDL-cholesterol values were lower (P = 0.011) in Indians and Pakistanis than in Americans. Multiple regression analysis indicated that approximately 18% of the variance in total cholesterol (P = 0.0010) and LDL cholesterol (P = 0.0009) was accounted for by ethnicity, energy expenditure, and the ratio of the sum of central to the sum of peripheral skinfold thicknesses. Ethnicity, sum of central skinfold thicknesses, ratio of polyunsaturated to saturated fat, and monounsaturated fat intake accounted for approximately 43% of the variance in triacylglycerol concentration (P < 0.0001). Monounsaturated fat, percentage body fat, and alcohol intake accounted for approximately 26% of variance in HDL cholesterol. Ethnicity contributed approximately 22% of the 25% overall variance in lipoprotein(a). CONCLUSIONS: Results suggest that these Indian and Pakistani women are at higher CVD risk than their American counterparts, but that increasing their physical activity is likely to decrease overall and regional adiposity, thereby improving their serum lipid profiles.

Breast cancer risk factors in two distinct ethnic groups: Indian and Pakistani vs. American premenopausal women.

Asian Indians from the Indian subcontinent have low rates of breast cancer, but studies on breast cancer risk factors in Indian and Pakistani women living in the United States are lacking. This study contrasted breast cancer risk factors [serum total 17 beta-estradiol (E2), sex hormone-binding globulin-bound E2, available E2, estrone (E1), and dehydroepiandrosterone sulfate, reproductive history, family history of cancer, body composition/size, dietary intake, physical activity, and excretion of isoflavones] between two distinct ethnic groups of premenopausal women residing in the United States. We also determined the contribution of these and other factors to the variability of each sex hormone. Distributions of values for serum total E2, available E2, and sex hormone-binding globulin-bound E2 (%) were greater (p < 0.005) in American (n = 47) than in Indian and Pakistani (n = 47) women. Multiple regression analysis indicated that 26% of the variability (p < or = 0.0001) in serum E2 was accounted for by the ratio of total cholesterol to high-density-lipoprotein cholesterol, length of time in the United States, and saturated fat intake, whereas less (17%) variability was accounted for by available E2 (representing free E2 + albumin-bound E2), contributed by the ratio of total cholesterol to high-density-lipoprotein cholesterol and saturated fat intake. Five variables accounted for 31% of the variability (p < or = 0.0001) in E1. The major finding of this study was that circulating sex hormone concentrations were determined more by environmental factors than by ethnicity, which was not a significant contributor to any of the serum hormones.