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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Menopause. Author manuscript; available in PMC 2008 May 5.
Published in final edited form as:
PMCID: PMC2366994
NIHMSID: NIHMS46093

Effects of soy protein isolate and moderate exercise on bone turnover and bone mineral density in postmenopausal women

Abstract

Objective

The aim of this study was to assess the independent and additive effects of soy protein isolate (SPI) and moderate-intensity exercise (EX) on bone turnover and bone mineral density (BMD).

Design

This study used a placebo-controlled, double-blind (soy), randomized 2 (SPI vs milk protein isolate [MPI]) × 2 (EX vs no EX) design. Sixty-one postmenopausal women were randomized, and 43 (62 ± 5 y) completed the 9-month intervention (SPI, n = 10; MPI, n = 12; SPI + EX, n = 11; MPI + EX, n = 10). Serum C-terminal cross-linked telopeptides of type I collagen and serum bone-specific alkaline phosphatase were measured as markers of bone resorption and formation, respectively. BMD was measured by dual-energy x-ray absorptiometry.

Results

At 9 months, SPI reduced serum C-terminal cross-linked telopeptides (−13.3% ± 15.3% vs −1.5% ± 21.0%; P = 0.02) and serum bone-specific alkaline phosphatase (−4.7% ± 14.7% vs 6.5% ± 17.7%; P = 0.02) compared to milk protein isolate. EX attenuated the reduction in serum C-terminal cross-linked telopeptides (−1.9% ± 21.6% vs −12.4% ± 15.3%; P = 0.04); however, no EX effects were apparent in serum bone-specific alkaline phosphatase at 9 months (2.8% ± 16.1% vs −1.0% ± 18.3%; P = 0.28). Neither SPI nor EX affected BMD at any site; however, change in BMD was related to change in fat mass (r = 0.40, P < 0.05).

Conclusions

In postmenopausal women (1) SPI reduces bone turnover with no impact on BMD over 9 months; (2) moderate-intensity endurance exercise training did not favorably alter bone turnover and had no impact on BMD; and (3) there were no additive effects of soy and exercise on bone turnover or BMD.

Keywords: Endurance training, Phytoestrogens, Clinical trial

Phytoestrogens, naturally occurring plant molecules such as isoflavones, lignans, and coumestans, have estrogenic and antiestrogenic activity in mammalian tissue.1 The preferential binding of isoflavones to estrogen receptor β indicates that they act as selective estrogen receptor modulators.2 Many postmenopausal women elect to use natural alternatives to estrogen therapy, and because isoflavones are present in abundance in soy protein,3 soy is a popular choice in this population.4

Although bone mineral density (BMD) is the most established marker for nontraumatic fracture risk, bone turnover has also been shown to be an independent predictor of fracture risk.5 A double-blind, randomized, controlled trial determined that 3 months of soy protein (40 g/day) containing isoflavones decreased bone resorption compared to a milk protein regimen.6 In contrast, several clinical trials using various formulations of soy protein isolate (SPI) found no clinically meaningful effects of soy on markers of bone metabolism.79 Several clinical trials have demonstrated a positive effect of soy protein or isoflavones on BMD,1014 but the findings have not been universal.15,16 Thus, the effect of soy on bone metabolism has been inconsistent.

The importance of physical activity at all stages of life for optimal bone health is well established.17,18 Specifically, bone tissue adapts to joint and ground reaction forces in a dose-dependent manner in the presence of adequate nutrition and hormone milieu,17,19 and several studies have established that midlife and older women maintain the ability to increase BMD in response to exercise training.2025 Furthermore, recent studies have suggested that the favorable effect of endurance exercise (ie, walking) on BMD may be related to a reduction in bone turnover.26,27 Several studies suggest that the addition of estrogen therapy to the exercise regimen confers additive effects on BMD.21,25 Additionally, in a mouse model, the additive effects of soy isoflavones and moderate treadmill exercise have been found to be as robust as β-estradiol treatment for preventing decreases in BMD after ovariectomy.28

In this context, the primary purpose of this study was to determine the independent and combined effects of SPI and endurance exercise on markers of bone resorption and formation and BMD in postmenopausal women. Importantly, we selected an exercise regimen and a soy dietary regimen that were reasonable from a public health perspective and were commonly used by many postmenopausal women for their assumed health benefits. We hypothesized that both SPI and exercise would reduce bone turnover in an independent and additive manner. Moreover, we anticipated that SPI and exercise would independently increase BMD and that the combined effects of SPI and exercise would elicit significant increases in BMD over the duration of the study (9 months).

METHODS

Participants

To be eligible for inclusion, women were at least 2 years past menopause, defined as time since last menstrual period. In addition, participants were (1) free of habitual soy protein or soy food usage; (2) free of hormone therapy use for at least 1 year; (3) aged 50 to 65 years; (4) willing and able to be randomized to a moderate-intensity supervised exercise program; (5) free of contraindications for estrogen use (eg, breast cancer, history of thromboembolism); (6) nonsmoking; (7) free from known metabolic or cardiovascular disease, such as type 2 diabetes mellitus, hypertension, or ischemic heart disease; and (8) not taking medications known to alter bone metabolism (eg, bisphosphonates). Participants were screened with a medical history, physical examination, standard blood chemistry evaluation, and a graded treadmill exercise stress test to identify those with ischemic heart disease. Informed consent was obtained from all participants before enrollment in the study, which was approved by the Washington University Human Studies Committee and General Clinical Research Center Scientific Advisory Committee.

Study design and randomization

A 2 (SPI vs milk protein isolate [MPI]) × 2 (exercise [EX] vs no EX) study design was used, with participants randomized into four groups: (1) SPI, (2) MPI, (3) SPI + EX, and (4) MPI + EX. Group assignment was based on a random number–generated table. The soy arm of the trial was conducted in a double-blind manner with protein products given a code. A research coordinator not involved with data collection or analyses potentially affected by subjectivity (eg, dual-energy x-ray absorptiometry [DXA] analysis) maintained the randomization log.

Dietary intervention

After expressing interest in study participation but before baseline testing, potential participants were provided with samples of protein beverage products to determine palatability. After randomization, participants received monthly supplies of the protein beverage products with instructions to consume one serving each day, which provided 25.6 g of protein and 91.2 mg aglycone units of isoflavones (or 0 isoflavones for MPI). The SPI and MPI products were formulated to be the same in energy, macronutrient, and micronutrient content, including 900 mg of calcium and 125 IU of vitamin D. To maintain energy intake, participants were specifically instructed to incorporate the products into their normal daily eating regimen as a protein substitute and not to add the products as a supplement to their normal dietary intake. Recipes and serving ideas were provided; however, no other dietary advice was given. The SPI and MPI products were provided by The Solae Company, St. Louis MO.

Exercise intervention

Participants randomized to the EX groups attended supervised endurance exercise 3 days per week for 9 months. Allowing for minor illness or travel, the entire program was completed within 10 months. The endurance exercise training program began at an intensity of 55% to 60% of peak aerobic capacity (VO2peak) and progressed gradually to 75% to 80% of VO2peak within 4 to 6 weeks depending on individual tolerance. Similarly, exercise duration was increased to approximately 45 minutes during that same time frame. Participants were permitted to rest when changing exercise mode; however, rest periods were discouraged after initial conditioning occurred. A variety of exercise modes were used, including a four-lane 17-lap per mile indoor track, treadmills, rowing ergometers, and stair-climbing ergo-meters. The exercise modes were individualized on the basis of participant preferences, abilities, and orthopedic capabilities. Participants were encouraged to use more than one mode to minimize joint pain, muscle fatigue, and boredom. Participants randomized to the no EX groups were asked to maintain their usual level of physical activity.

Anthropometric measures

Standing height was measured to the nearest 0.1 cm with a stadiometer. Body weight was measured on a balance scale with participants wearing a light-weight hospital gown.

Biochemical markers of bone metabolism

To minimize diurnal variance, all blood samples were obtained in the morning between the hours of 7:00 and 9:00 AM after an overnight fast. All samples were stored at −80°C for subsequent batch analysis in the University of Kentucky GCRC Core Biochemical Analysis Laboratory. Serum C-terminal cross-linked telopeptides of type I collagen (S-CTX) (Serum CrossLaps Assay, Nordic Bioscience Diagnostics, Herlev, Denmark) was measured as a marker of bone resorption. Serum bone-specific alkaline phosphatase (S-BSAP) (Immuno-capture Assay, Quidel Corporation, San Diego, CA) was measured as a marker of bone formation. Intra-assay precision of measurement for these markers by enzyme-linked immunoassay ranges from 1.4% to 2.8% in this laboratory.

BMD and body composition

For body composition and bone mineral measures, participants wore a hospital gown and removed all jewelry and all other clothing except underwear. Bone mineral content (BMC), density, and whole-body fat and lean mass were measured by DXA using a Hologic QDR 1000 bone densitometer (software version 5.73, Bedford, MA). Scans of the total body, lumbar spine, and nondominant proximal femur were done. The short- and long-term accuracy of the densitometer was verified by scanning a manufacturer’s hydroxyapatite spine phantom of a known density. The precision of DXA measurements of interest is 1.5% to 2% in this laboratory.29

Maximal aerobic power and stress test

Graded treadmill exercise tests were conducted to measure (1) heart rate, blood pressure, and electrocardiographic responses to exercise to determine study eligibility and (2) peak aerobic power (VO2peak) as an indication of training adaptation. Participants walked on a treadmill at the fastest comfortable pace at 0% grade for 3 to 4 minutes, after which the grade increased by 1% to 2% every 1 or 2 minutes. The test continued until the participants were unable to continue because of volitional exhaustion, electrocardiographic changes, or other abnormalities that rendered it unsafe to continue to exercise. Oxygen uptake was measured continuously using open-circuit spirometry as previously described.30

Dietary intake

Three-day (2 weekdays and 1 weekend day) food diaries were used to estimate energy intake and diet composition. The research dietitian instructed each participant to record all food and beverages consumed, preparation methods, and approximate portion sizes in the food diaries at the time of consumption (rather than from recall at the end of the day, which would reduce accuracy). Upon completion of these food diaries, the research dietitian met individually with each participant to review the diaries and to fill in any missing information. Total energy, macronutrient, and micronutrient contents were determined using Nutritionist Pro nutrition analysis software (First DataBank, San Bruno, CA).

Statistical analysis

All data analyses were conducted using SPSS version 12.0 (SPSS, Inc., Chicago, IL). Means, SDs, and distribution statistics (skewness and kurtosis) were evaluated to ensure that assumptions of normality were met for subsequent analyses on primary outcomes. Differences among groups in baseline measurements were evaluated using one-way analysis of variance. Because of the preliminary nature of this pilot study, the physiological response of the soy and exercise treatments was of primary interest. Therefore, the primary analysis was a per-protocol analysis using data from all individuals who completed the trial; however, an intention-to-treat analysis was also conducted on the primary outcomes, markers of bone turnover and BMD, using data from all randomized individuals. For the intention-to-treat analysis, missing data due to lack of follow-up was determined using the last value carried forward approach. The primary analyses used a two-way analysis of variance (soy × exercise) to test for an interaction and for main effects of the soy and exercise treatments on outcomes of interest. Primary outcomes were changes from baseline in response to the 9-month intervention in S-CTX, S-BSAP, and BMD. Secondary outcomes included 9-month changes from baseline in dietary intake, VO2peak, and fat and lean mass. Main effects were considered when interactions were not significant. Within-group post hoc comparisons were made using paired sample t tests. Pearson correlations were used to determine the relationship of potential confounding variables (eg, fat mass change) with primary outcomes. Such confounding variables were then entered as covariates into the analysis of variance model as indicated. A P value less than 0.05 was considered significant. Data are presented as means ± SDs except in the figures, which present means ± SEs.

RESULTS

Sixty-one postmenopausal women were randomized, and 43 (62 ± 5 y) completed the 9-month trial in the following four groups: SPI, n = 10; MPI, n = 12; SPI + EX, n = 11; and MPI + EX, n = 10. As expected, dropout rates were higher in the EX groups (n = 12) than the no EX groups (n = 6) because of the time commitment. However, no differences in dropout rates were observed between the SPI (n = 9) and MPI (n = 9) groups.

Participant characteristics

Although at baseline the MPI + EX group was younger and was fewer years past menopause than the other groups, there were no significant differences among the groups in age, menopausal status, fitness, or body composition (Table 1).

TABLE 1
Baseline characteristics (mean ± SD)

Dietary intake

Total energy intakes were similar among the groups at baseline and in response to the interventions. Energy intake was 1,854 ± 331 kcal/day at baseline and 1,925 ± 344 at 9 months (P > 0.05 for all group changes). No significant difference in macronutrient intake was evident in response to the intervention except for a significant (all groups P < 0.05) increase in protein intake, which was similar among the groups (changes ranged from + 15 to + 23 g/day). No group differences were apparent in baseline values (data not shown) or change in dietary calcium (average change: +834 ± 280 mg, P = 0.66) and vitamin D intake (average change: +115 ± 80 IU, P = 0.82) in response to the interventions. The groups appeared to have an adequate dietary calcium intake, averaging 1,582 ± 382 mg/day, per protocol.

Endurance-exercise training

There was no interaction between soy and exercise treatments on fitness changes (P = 0.35). There was a main effect of exercise on VO2peak (P < 0.001) such that EX groups improved (12.2%, P = 0.001) and no EX groups reduced (−5.7%, P = 0.085) cardiorespiratory fitness during the 9-month intervention. No main effect of soy (SPI vs MPI) was evident (P = 0.45). Although the MPI + EX group increased their VO2peak by 16% and the SPI + EX group increased VO2peak by 8.5%, suggesting differing training intensities, this difference was not statistically different.

Body composition

No interaction (P = 0.15) or main effects for soy (P = 0.38) or exercise (P = 0.10) occurred for weight change in response to the 9-month intervention (Table 2). There were no significant interactive (P = 0.12) or main effects of soy (P = 0.86) and exercise (P = 0.74) treatments on changes in fat mass. However, in the absence of an interaction (P = 0.84), exercise reduced lean mass (P = 0.001), and there was a trend for soy to increase lean mass (P = 0.06).

TABLE 2
Effects of soy and exercise on weight and body composition after 9 months (mean ± SD)

Serum markers of bone turnover

Results from the per-protocol analysis (N = 43) determined that there were no significant interactions between soy and exercise on serum markers of bone resorption (P = 0.74) or formation (P = 0.95) in response to 9 months of treatment (Table 3, P Fig. 1). There was a significant main effect of soy ( = 0.02) and exercise (P = 0.04) on S-CTX at 9 months; however, whereas soy resulted in a favorable reduction in bone resorption, exercise seemed to attenuate the reduction in bone resorption, with the latter effect being driven by the nonsignificant 7.4% ± 21.9% (P = 0.29) increase in the MPI + EX group. Within groups, there was a significant reduction in S-CTX in SPI (−15.7% ± 12.8%, P = 0.004) and a trend for a reduction in MPI (−9.7% ± 17.1%, P = 0.08) and SPI + EX (−11.2% ± 17.6%, P = 0.06) from baseline at 9 months. The main effect of soy on S-CTX remained unchanged after controlling for changes in fat mass or years postmenopausal. However, the main effect of exercise on S-CTX became nonsignificant after adjusting for either changes in fat mass (P = 0.07) or years past menopause (P = 0.09).

FIG. 1
Percentage of changes from baseline in markers of bone resorption (serum C-terminal cross-linked telopeptides of type I collagen [S-CTX]) and bone formation (serum bone-specific alkaline phosphatase [S-BSAP]) in response to exercise and/or supplementation ...
TABLE 3
Main effects of soy and exercise on absolute changes in bone mineral density and markers of bone turnover after 9 months

Results from the intention-to-treat analysis (N = 61) on soy and exercise effects on change in S-CTX were similar in direction, but the statistical significance changed. Similar to the per-protocol analysis, there were no significant interactions between soy and exercise (P = 0.75); however, the main effects of soy (mean ± SD, −0.05 ± 0.19 vs 0.00 ± 0.11 ng/mL for SPI and MPI, respectively; P = 0.22) and exercise (0.00 ± 0.20 vs −0.06 ± 0.08 ng/mL for EX and no EX, respectively, P = 0.12) on serum markers of S-CTX were no longer apparent.

With regard to bone formation, using the per-protocol analysis (N = 43), there was a significant main effect of soy (P = 0.03) with soy reducing S-BSAP. No main effect of exercise (P = 0.28) on S-BSAP was apparent. Within groups, there was a trend for an increase in S-BSAP in MPI (8.6 ± 14.2%, P = 0.08) from baseline at 9 months. Similar to the S-CTX results, the intention-to-treat analyses (N = 61) for S-BSAP were similar in direction, but the statistical significance changed. Similar to the per-protocol analysis, there were no significant interactions between soy and exercise (P = 0.87) and no significant impact of exercise (mean ± SD, 1.0 ± 5.7 vs −0.76 ± 4.5 U/L for EX and no EX groups, respectively, P = 0.18); however, the main effects of soy (−0.9 ± 5.8 vs 1.2 ± 4.3 U/L for SPI and MPI, respectively, P = 0.11) on serum markers of S-BSAP were no longer apparent.

BMD

At baseline, there were no significant differences among the groups in BMD at any site measured (Table 1). Using the per-protocol analysis (N = 43), at 9 months, there was no significant interaction or main effects of soy or exercise on BMD at any site (all P > 0.05; Table 3, Fig. 2). Using the intention-to-treat analyses (N = 61) did not alter the BMD results, with all effects remaining nonsignificant (all > 0.05).

FIG. 2
Percentage of changes from baseline in bone mineral density (BMD) of the whole body, lumbar spine, and proximal femur in response to exercise and/or supplementation with soy over 9 months. MPI, milk protein isolate; SPI, soy protein isolate; EX, exercise. ...

In the collective sample (N = 43), change in total body mass was significantly related to change in lumbar spine and proximal femur BMD (r = 0.36 and 0.34, respectively; P = 0.02). Similarly, change in fat mass was significantly related to change in lumbar spine (r = 0.40, P = 0.01) and proximal femur BMD (r = 0.40, P = 0.008). Nevertheless, the main effects of soy and exercise on BMD remained unchanged after controlling for changes in total body mass and fat mass using analysis of covariance. Change in lean mass was not related to change in lumbar spine BMD (r = 0.00) or proximal femur BMD (r = −0.07).

DISCUSSION

The primary findings of this investigation assessing the independent and combined effects of soy protein and exercise in postmenopausal women were (1) dietary supplementation with soy improved markers of bone turnover (ie, decreased bone resorption and formation) in the absence of a change in BMD; (2) moderate-intensity endurance exercise training did not favorably alter bone resorption and had no impact on BMD; and (3) there were no apparent additive or synergistic effects of soy and exercise on markers of bone turnover or BMD. To our knowledge, this is the first study to evaluate the combined effects of soy and exercise treatments on markers of bone turnover and BMD in postmenopausal women.

Our findings are in agreement with those of Arjmandi et al,6 who determined that 3 months of soy protein (40 g/day) decreased bone resorption compared to milk protein in postmenopausal women of similar age to those women in the current study. However, in contrast to our findings, several other trials conducted in postmenopausal women of various intervention lengths and soy intakes have reported no effect of soy on markers of bone turnover.79

Our findings that soy protein did not favorably affect BMD is in contrast to work by Potter et al,10 who determined that 6 months of SPI containing 90 mg/day of isoflavones significantly increased lumbar spine BMC and BMD by approximately 2.3% compared to SPI containing 56 mg/day of isoflavones or a casein and nonfat dry milk placebo in postmenopausal women aged 39 to 83 years with high variation for years past menopause. Our findings are also in contrast to work by Alekel et al,11 who determined that isoflavones contained within soy protein (approximately 80 mg/day of isoflavones) and isoflavone-free soy protein were both effective in preserving BMD in perimenopausal women compared to whey protein over 6 months. Although changes in bone turnover were negatively related to the percentage of changes in BMD and BMC, there was no group effect in BSAP. Finally, ingesting 76 mg/day of isoflavones delivered in soy milk for 2 years prevented lumbar spine loss in postmenopausal women at high risk of or with established osteoporosis.14

Our data correlates well with studies that have not found favorable changes in BMD in response to soy or isoflavones.31 Soy protein containing 96 mg/day or 52 mg/day of isoflavones did not affect BMD of the spine or femoral neck over 15 months in early postmenopausal women.15 Similar results were determined from a 1-year study comparing older postmenopausal women (60–75 y) randomized to ingest 25 g/day of soy protein (containing 99 mg/day of isoflavones) or 25 g/day of milk protein delivered in powder form.16

The potential for soy protein or isoflavones to alter bone metabolism as evidenced from DXA measures or bone metabolism markers is at present inconclusive.32 This lack of consensus in the literature is undoubtedly related to the variation in study design as studies used different delivery mechanisms (ie, soy protein isolate, whole soy foods, extracted isoflavones) known to alter bioavailability of the soy components,33 different populations (perimenopausal, early or late postmenopause), and different study designs (duration of intervention, dosage, bone marker selection, and timing of sampling).

The importance of physical activity at all stages of life for optimal bone health is well established.17,18 Several studies determined that midlife and older women clearly maintain the capacity to enhance BMD at clinically relevant sites given an adequate stimulus via a targeted loading exercise regimen.2025 Additionally, data suggest that the addition of estrogen therapy to the exercise regimen confers additive effects on primary bone outcomes.21,25 Lower intensity/impact exercise has been shown to have minimal effects on BMD in postmenopausal women34; however, favorable changes were determined in postmenopausal women who were osteopenic or osteoporotic in response to 12 months of low-intensity walking 60 minutes 4 days per week.26 These findings have high public health importance as the majority of midlife and older women are unable to overload their skeleton to the degree required to enhance BMD due to orthopedic limitations, especially if already deemed at high risk for fracture.

The impact of habitual exercise on markers of bone metabolism is less established. For example, work by Kohrt et al21 determined that 9 months of weight-bearing exercise did not affect osteocalcin and insulin-like growth factor I levels but did invoke significant increases in BMD. More recent evidence suggests that targeted loading composed of jumps and resistance training increased BMD in the absence of a change in bone resorption and formation over 2 years in early postmenopausal women.34 However, no time-course data (ie, only baseline and 24-month data) for this trial were presented, so true evaluation of bone turnover response to the intervention is not possible. Other reports in this population suggest that moderate-intensity exercise ameliorates increased turnover,27 which was seen as early as 3 months into the program.26

Depending on type of exercise program (ground reaction or joint reaction forces; endurance or strength mode), the effect of exercise on bone may be modulated by changes in fat mass. Increased body weight is protective for bone mass and fracture risk in postmenopausal women.17 Weight loss in older women has been implicated in bone loss and linked to increased fracture risk35 with documented changes in bone turnover.36 Estrogen status has been shown to affect bone loss in response to weight loss.37 The postulated mechanism regarding this bone loss is that adipose tissue is an important site of estrogen production via the aromatization of androgens.38 Recent evidence suggests that when weight loss is modest (approximately 4.0 kg) and is primarily mediated through exercise and not dietary restriction, estrogen protects against reductions in BMD.39 Although speculative, it is possible that reductions in fat mass with training blunted any potential effect of the modest strain overload with the exercise program or the estrogenic effects of SPI. This theory is supported in the current study by the positive significant relationships between change in fat mass and change in BMD at the lumbar spine and proximal femur sites.

This pilot study was designed to assess the effects of soy protein combined with exercise on bone turnover and BMD. As such, the study design used was similar to studies previously conducted by our group that investigated the independent and combined effects of estrogen therapy and exercise on bone health in postmenopausal women.21 Although these preliminary data are of use to other research teams planning additional investigations in the area of soy protein, exercise, weight change, and bone health, our results should be interpreted with caution because of a number of limitations of this pilot study that should be considered. First, our sample size was small given the estimated effect size for soy and exercise interventions on BMD; however, this was not the only factor to influence statistical significance of the BMD outcomes as effect size and treatment response variability affect statistical power. For example, the calculated effect size of the soy main effect on proximal femur BMD was 0.13 (Cohen’s d = change in BMD/SD of change in BMD), which is a very small effect and would require approximately 100 participants per group to determine statistical significance of treatment. The calculation of an effect size from this preliminary investigation (1) assists the planning of future research with regard to effect size and (2) allows insight into the clinical significance of this treatment.

Second, the length of the intervention may also have affected the effect size of soy treatment on BMD. Because markers of bone turnover predict changes in BMD and the soy supplement decreased bone turnover, we cannot exclude a positive effect of soy on BMD with a longer follow-up period. The soy treatment attenuated reductions in whole-body and lumbar spine BMD and increased proximal femur BMD compared to the milk protein treatment. Although not significant, an attenuated loss can be viewed as a favorable treatment response in this cohort that reduces BMD by approximately 1% to 2% per year. Additionally, because markers of bone turnover predict subsequent risk of hip fracture independently of BMD,5 a reduction in bone turnover (ie, decrease in S-CTX and S-BSAP) in response to SPI in our participants can be interpreted as a favorable effect on bone health.

Third, the exercise intervention was not specifically designed to maximize loading forces (ie, high-impact exercises) to mechanically stress bone and induce changes in BMD but rather as a moderate-intensity exercise regimen more typically performed by postmenopausal women. Thus, the lower intensity exercise regimen likely reduced the effect sizes for exercise on BMD and markers of bone turnover.

Fourth, we did not implement strict dietary control and did not adequately sample dietary intake (baseline and 9 months). This design consideration was due to the primary focus of the trial being to test the effectiveness of the phytoestrogen properties of SPI on bone health and not to investigate a nutritional manipulation per se. Notably, although participants were instructed to consume the protein products on a daily basis and strive for weight maintenance, little nutritional support was given. Dietary changes occurred in all groups, including increases in calcium, vitamin D, and protein intake. Recent literature suggests that increases in protein intake in the presence of adequate calcium intake is beneficial for bone health in the elderly40; therefore, the changes in calcium and dietary protein intake that occurred in all treatment groups may have modulated the impact of the soy treatment in this study.

Finally, experts in the phytoestrogen field contend that the intestinal metabolism of isoflavones may strongly influence the clinical efficacy of soy foods to effect bone loss. Specifically, preliminary evidence has shown that a bacterial metabolite of daidzein, equol, which is not found in soy, has been shown to modulate the effect of soy on bone metabolism. Postmenopausal women who were equol producers (45% of sample studied) increased lumbar spine BMD 2.4% compared to nonproducers in response to a soy intervention.31 Although available subjective data indicate that adherence to the protein supplement was approximately 90%, objective phytoestrogen and specifically equol data are not available for the current study.

CONCLUSIONS

In conclusion, although the additive effects of SPI-containing isoflavones and moderate exercise have been found to be as strong as β-estradiol estrogen to prevent bone loss in ovariectomized mice,28 the results from this 9-month soy protein and exercise intervention in postmenopausal women are less encouraging. Even though SPI reduced bone turnover, there was no evidence of a corresponding positive effect on BMD. Exercise training did not favorably affect bone turnover or BMD. However, the relatively small sample size, short duration of the intervention, and low-intensity exercise all likely affected the null effect of the soy and exercise interventions on BMD.

Acknowledgments

Funding/support: Supported by grants from The Solae Company (St. Louis, MO). Dr. Evans was supported by Institutional National Research Service Award (NRSA) AG-00078 and Individual NRSA AG-05874. Dr. Van Pelt was supported by Institutional NRSA AG-00078 and Individual NRSA HL-10249. This study was supported by the Washington University Claude D. Pepper Older American Independence Center, grant AG-13629, General Clinical Research Center grant RR-00036, and Diabetes Research and Training Center grant DK-20579. Markers of bone metabolism were supported by the University of Kentucky General Clinical Research Center, grant M01-RR-02602.

Footnotes

Financial disclosure: None reported.

References

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