Prevention of bone loss after withdrawal of tamoxifen

Abstract

Objective: Tamoxifen has antiestrogenic effects in the breast and estrogenlike activity in the skeletons of postmenopausal women. We hypothesized that postmenopausal women with breast cancer would experience a rapid decline in bone mineral density (BMD) after stopping tamoxifen, similar to that seen with estrogen withdrawal. The objective of this study was to assess, in a randomized, double-blind, placebo-controlled trial, whether administration of alendronate (70 mg weekly) would prevent bone loss associated with tamoxifen discontinuation.

Methods: Postmenopausal women with breast cancer were randomly assigned to receive alendronate or placebo for 1 year within 3 months after withdrawal of tamoxifen therapy. We initiated a randomized, double-blind, placebo-controlled trial of alendronate (70 mg weekly) in an effort to prevent bone loss associated with discontinuation of tamoxifen therapy. Patients treated with aromatase inhibitors were excluded from the study. BMD at the spine, hip, and forearm was measured at baseline and at 12 months. Analyses employed repeated-measures analysis of variance.

Results: Patient accrual was considerably limited by the substantial increase in use of aromatase inhibitors during the enrollment period. The study patients (N = 11) had similar baseline BMD T-scores in the alendronate (n = 6) and placebo (n = 5) subgroups. After 1 year, tamoxifen withdrawal was associated with a significant decline in BMD at the femoral neck, which appeared to be prevented by weekly administration of alendronate (-5.2% versus 0.1%; P = .02). Levels of urinary N-telopeptide, a marker of bone turnover, increased by 48% in study subjects in the placebo group (P < .01), whereas weekly alendronate treatment was associated with a 52% decline (P < .01) in this bone resorption marker.

Conclusion: Differences in BMD and bone turnover were evident despite the small sample size. These data suggest that postmenopausal women with breast cancer completing tamoxifen therapy warrant an evaluation of their skeletal health and that bisphosphonate therapy may be useful in preventing bone loss associated with discontinuation of tamoxifen.

Fig. 1

Change in bone mineral density (BMD) 1 year after withdrawal of tamoxifen in the alendronate- and placebo-treated study groups. *The treatment group had a significant effect only on change in femoral neck BMD from baseline (P = .02). Results are shown as mean values ± SEM.

Fig. 2

Change in bone mineral density at the femoral neck during the 12-month study period, shown for each patient in the alendronate- and placebo-treated study groups.

Fig. 3

Urinary N-telopeptide at baseline and 1 year after withdrawal of tamoxifen in the alendronate-and placebo-treated study groups. The treatment group had a significant effect on change in urinary N-telopeptide from baseline (P < .001). Bracket lines and P values describe within-group change from baseline. Results are shown as mean values ± SEM. BCE = bone collagen equivalents; Cr = creatinine.