555 Background: The LEAP trial is an open, randomized, multicenter, Phase I pharmacodynamic study comparing the effects of the AIs L, E and A on safety parameters, such as serum markers of bone formation and resorption, lipid profiles, and adrenal function in healthy postmenopausal women with normal bone mineral density at the spine and hip. Elevated bone biochemical levels indicate high turnover of bone, and correlate with a loss in bone mineral density. It has been suggested that there are differences between the effect of the steroidal AIs (E) and non-steroidal AIs (A and L) on bone turnover, with steroidal AIs having a less negative effect. Methods: Healthy volunteersfrom the UK and Hungarywere randomized to receive A (1 mg/day), L (2.5 mg/day), or E (25 mg/day) orally, once daily for 24 weeks. Changes from baseline in log-transformed bone alkaline phosphatase (ALP), serum C-telopeptide crosslinks (CTX), parathyroid hormone (PTH) and propeptide of type I procollagen (PINP) at 24 weeks on A, were compared with those on L and E by ANCOVA, adjusting for treatment, baseline measurement, BMI, smoking status and baseline estradiol. No adjustments were made for multiple comparisons. Results: A total of 102 healthy volunteers were recruited, with 90 participants evaluable at 24 weeks (29 A, 29 L, 32 E). Participant demographics were similar between the treatment groups in terms of age, years since menopause, and history of hysterectomy and oophorectomy. Bone biochemical measurement changes are presented in the table . With the exception of PTH, where there is a greater decrease in PTH with E than with A (p=0.04), there were no statistically significant differences between the AIs. Conclusions: The steroidal and non-steroidal AIs appear to have similar effects on bone biochemical measurements, and thus bone turnover. All three licensed AIs result in increases in bone turnover. [Table: see text] [Table: see text]