ORIGINAL ARTICLESoy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized controlled trials
Introduction
With increases in life expectancy, osteoporosis has become a common disease in post-menopausal women. Although hormone replacement therapy is the first choice of treatment for hormone-related osteoporosis, results of randomized controlled trials (RCTs) of this treatment are contradictory. In the Heart and Estrogen/Progestin replacement study, hormone replacement therapy for a mean of 4.1 years did not show bone protection or a significant reduction in the risk of hip fracture.1 On the other hand, the Women's Health Initiative trial, a famous RCT in this field, found a 24% reduction of total fracture and 23% reduction of other osteoporotic fractures after the treatment with estrogen plus progestin.2 However, there was no net benefit in that study when considering the effects of hormone therapy on other important disease outcomes in a global model, even in women considered to be a high risk of fracture.2 Thus, compliance with such treatment is generally very poor because hormone replacement therapy has some negative side effects such as an increased risk of cardiovascular disease and breast cancer.3 Therefore, new bone protection options are needed.
In recent years, isoflavones have received considerable attention in the medical and scientific literature. Some cross-sectional studies conducted in Asian populations reported significantly positive associations between soy protein or isoflavone intakes and bone mineral density.4, 5 It is well known that the incidence of osteoporosis-related fracture is significantly lower in Southern and Eastern Asian women than in Western women.6 One possible reason for this difference is high intake of phytoestrogens; Asian peoples consume soy 10–20 times more than Western peoples.7 Soy isoflavones comprise mainly genistein, daidzein, and glycitein, which have structures similar to that of 17β-estradiol, a potential alternative to hormone replacement therapy.8 However, the effects of isoflavones on bone mass appear inconsistent in RCTs, ranging from no significant changes to a slight increase in bone mineral density. Thus, a statistical method of combining these diverse data is needed to evaluate the usefulness of isoflavone therapy. Meta-analysis combines or integrates the results of several studies to provide increased statistical power for the quantitative identification of trends.9 In the RCTs, spine bone mineral density (SBMD) and spine bone mineral content (SBMC) were generally measured as bone mass markers. Therefore, we identified all RCTs related to the effects of isoflavones on SBMD or SBMC and analyzed the effects of isoflavones on bone mass quantitatively.
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Materials and methods
MEDLINE (January 1966–September 2006), the Cochrane Controlled Trials Register, EMBASE (1985–January 2006), Science Citation Index and PUBMED (updated till September 2006), China National Knowledge Intrastructure (CNKI, 1979–September 2006) were used to search articles that described RCTs investigating the effect of isoflavones on bone mass. Titles, abstracts, and subject headings in the databases were searched with the use of the following keywords: bone, osteoporosis, bone mass,
Results
The trial flow chart was illustrated in Figure 1. Our literature search identified 33 RCTs. Twenty-three studies were excluded because of lack of indices of interest, non-randomization, lack of a control group, insufficient original data or baseline values. Thus, 10 studies with a total of 608 subjects were included in this meta-analysis.13, 14, 15, 16, 17, 18, 19, 20, 21, 22 The characteristics of the trials included were shown in Table 1. Six studies had quality score of five, three studies
Discussion
Of all skeletal sites measured, the spine is the area that is thought to be the most sensitive to estrogen because of its higher content of trabecular bone.23 The spine is remodeled more rapidly than the hip, which contains a higher proportion of cortical bone.24 In order to clarify the effect of isoflavone intake on the hip, we searched the articles and found only three studies, which is not enough for meta-analysis. Chen et al. reported that soy isoflavones have a mild, but significant effect
Conflict of interest statement
None declared.
Acknowledgments
Pei-Yu Wang and Ryohei Katoh participated in the design of this manuscript. De-Fu Ma and Li-Qiang Qin participated in abstracting the data and performing statistical analysis. All authors read and approved the final manuscript.
This research was supported in part by a grant from National Natural Science Foundation of China (No. 30471448) to Dr. Pei-Yu Wang.
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Contributed equally to the work.