ALIQUOT (
Anastrozole vs.
Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of
aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with
estrogen receptor-positive
breast cancer. Ninety-four patients were randomized to receive either 12 weeks of
letrozole (2.5 mg; n = 42) followed by 12 weeks of
anastrozole (1 mg), or 12 weeks of
anastrozole (1 mg; n = 42) followed by 12 weeks of
letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to
tamoxifen (n = 38) or continued on
anastrozole or
letrozole. In the beginning of the study, 42 patients had taken
tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including
bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior
tamoxifen therapy resulted in a significantly lower mean baseline
procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior
tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior
tamoxifen had significantly greater increases than patients with no prior
tamoxifen. Patients treated with 3 months of
tamoxifen following 6 months of an AI showed a significant decrease in markers of
bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time.
Anastrozole and
letrozole produce similar effects on bone metabolism and turnover. Stopping
tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in
tamoxifen-naïve patients. Patients given
tamoxifen following AI
therapy showed a decrease in markers of
bone resorption.