High phytoestrogen intake among Asian women has been thought to explain the low risk of bone fractures in these populations. In a randomized placebo-controlled trial we studied the effects of isoflavonoids on urinary output of the N-terminal cross-linked telopeptide of type I collagen, pyridinoline (Pyr), and deoxypyridinoline (Dpyr) (bone resorption markers) and serum levels of bone-specific alkaline phosphatase and N-terminal and C-terminal procollagen type I (bone formation markers). Fifty-five postmenopausal women with a history of breast cancer used phytoestrogens (114 mg of isoflavonoids) or placebo tablets daily for 3 months; the treatment regimens were then crossed over after a 2-month washout period. The markers were measured before and on the last day of each treatment period. Bone resorption was reduced during phytoestrogen use, as reflected in falls in the urinary output of Pyr (9%; P = 0.001) and Dpyr (5%; P = 0.008). Compared with the placebo group, the fall in Dpyr was significant (P = 0.022) and the falls in Pyr (P = 0.084) and N-terminal cross-linked telopeptide of type I collagen (P = 0.082) showed a trend toward significance. Bone formation markers were not affected by this regimen. Thus, isoflavonoid-induced inhibition of bone resorption may contribute to the low risk of osteoporosis in Asian women.