Adjuvant treatment of breast cancer with aromatase inhibitors has been associated with increased bone loss. In this study, postmenopausal patients with oestrogen receptor positive breast cancer were randomised to exemestane for 5 years or tamoxifen for 2-2.5 years, followed by exemestane for 2-2.5 years. Levels of bone formation markers (bone specific alkaline phosphatase, amino terminal propeptide of type I procollagen, osteocalcin), and the bone resorption marker (carboxyterminal crosslinked telopeptide of type I collagen), were assessed at baseline and after 3, 6 and 12 months of treatment. Exemestane (n=78) resulted in increases from baseline in all bone turnover marker levels at all timepoints. In contrast, levels of all bone marker turnovers decreased with tamoxifen (n=83). Differences between tamoxifen and exemestane were statistically significant for all bone turnover markers at all timepoints. In conclusion, exemestane results in increases in markers of bone formation and resorption, while decreases are observed with tamoxifen.