Bone Abstracts

Introduction: Bone mineral density (BMD) evaluations have shown that adjuvant chemotherapy or endocrine therapy (ET) for early breast cancer (BC) is associated with accelerated BMD loss and increased fracture risk. In recent studies, zoledronic acid (ZOL) increased BMD in premenopausal and postmenopausal women with BC, and improved disease-free survival in some patient subsets compared with no ZOL. The purpose of the current study was to investigate the effect of adjuvant treatment with ZOL on BMD in premenopausal women with early BC treated with chemotherapy or ET.

Methods: In this randomized, double-blind, placebo-controlled study, 71 patients receiving adjuvant chemotherapy and/or ET were randomly assigned to also receive ZOL (4 mg i.v. q 3 months) or placebo for 24 months. The primary endpoint was change in BMD at lumbar spine (LS) at 24 months relative to baseline. Secondary endpoints included change in femoral neck and total femoral BMD, course and change in bone turnover marker levels, assessment of potential correlations between BMD and bone turnover, development of metastases, pathologic fractures, and safety and tolerability.

Results: At 24 months, LS BMD substantially increased (+3.13%) with ZOL, and decreased (−6.46%) with placebo relative to baseline (P<0.001, between-group comparison). Femoral neck and total BMD also increased with ZOL, vs decreases with placebo at 24 months relative to baseline (P<0.001, between-group comparisons). By month 3, mean bone marker levels decreased (−65% for C-telopeptide of type I collagen and −61% for N-terminal propeptide of type 1 procollagen, relative to baseline) with ZOL, with significant (P<0.001) between-group differences in levels of both bone markers at 24 months vs baseline. Overall, ZOL was well tolerated, and only one case of osteonecrosis of the jaw was reported.

Conclusions: Early initiation of ZOL is well tolerated and preserves BMD and reduces bone turnover biomarker levels in premenopausal women with early BC undergoing chemotherapy or ET.