Effects of Phytoestrogens on Bone Turnover in Postmenopausal Women with a History of Breast Cancer

Author: Eini Nikander, Merja Metsa-Heikkila, Olavi Ylikorkala and Aila Tiitinen

Publication: The Journal of Clinical Endocrinology and Metabolism Vol. 89, No. 3 1207-1212.

Menopausal women have a higher risk of osteoporoses caused by low estrogen levels. Hormone replacement therapy migh help to reduce this risk of osteoporosis but there is also an increased risk of breast cancer. Asian women, who consume more phytoestrogens such as isoflavones, have a lower incidence of osteoporosis than Western women. Many studies have already illustrated that the soy isoflavones (gensitein and daidzein) have an effect on bone turnover and can improve bone health in animals:

  • Knight DC, Eden JA: A review of the clinical effects of phytoestrogens. Obstet Gynecol 87:897-904, 1966
  • Draper CR et al, Phytoestrogens reduce bone loss and bone resorption in oophorectomized rats. J Nutr 127:1795-1799, 1997
  • Murkies AL et al, Phytoestrogens. J Clin Endocrinol Metab 83:297-303, 1998
  • Arjmandi BH et al, Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr 68:1364S-1368S, 1998

The purpose of this study was to investigate the effects of isoflavones on bone turnover by measuring urinary excretion of bone resorption markers and serum levels of bone formation markers. The following bone resorption markers were measured: N-terminal cross linked telopeptide of type I collagen, pyridinoline and deoxypyridinoline. Serum levels were determined of bone-specific alkaline phosphatase and the collagen prpeptides N-terminal procallogen type I and C-terminal procallogen type I. The experiment was carried out on 55 postmenopausal women with a history of breast cancer. They were divided in a isoflavone group (114 mg isoflavones per day) and a placebo group. After a treatment period of 3 months the regimes were crossed over after a washout period of 2 months. The bone formation markers were measured at the start and end of each treatment period.

The researches found a significant decrease of bone resorption in the isoflavones group. The bone resorption markers pyridinoline and deoxypyridinoline were lower in the urinary excretions. Bone formation makers were not significantly influenced by the isoflavones, which could be explained by the short period of the experiment. The serum levels of the daidzein, genistein and equol were considerably higher in the isoflavones group. There was no correlation between the serum levels of genistein or equol and bone markers. The serum levels of daidzein were correlated with the fall in concentration of pyridinoline. The molecular mechanism by which isoflavones influence bone turnover is still unclear. Osteoblasts, which are responsible for bone formation, have estrogen receptors which can bind with isoflavones. Isoflavones could also increase calcium absorption and IGF-1 production. The isoflavone genistein is known to increase the production of osteoprotegerin by osteoblasts. Osteoprotegerin has been demonstrated to be a potent inhibitor of bone turnover.

The study concluded that the inhibition of bone resorption may contribute to the low risk of bone fractures in Asian women. This study was carried out with tablets containing the three soy isoflavones daidzein, genistein and glycitein. More studies are required to determine the effect of each these isoflavones on bone preservation.