Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer

Abstract

Purpose: Adjuvant chemotherapy for breast cancer (BC) may be associated with increased rates of bone loss and decreased bone mineral density (BMD) and may lead to premature osteoporosis and increased fracture risk. We examined whether zoledronic acid (ZA) prevents bone loss in premenopausal women receiving chemotherapy for early-stage BC.

Patients and methods: This study is a randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg intravenously every 3 months) versus placebo for 1 year. Premenopausal women underwent serial BMD measurements before initiating chemotherapy and at 6 and 12 months. The primary outcome was percent change in lumbar spine (LS) BMD at 6 months. Secondary outcomes were percent change at any BMD site and markers of bone turnover at 12 months. Linear mixed model analysis for repeated measures was performed.

Results: Of 101 women who were randomly assigned and completed baseline evaluation, 96 completed the 6-month evaluation, and 85 completed the 12-month evaluation. Baseline characteristics were comparable between the groups. Mean age was 42 years. Placebo was associated with significant decline in LS BMD at both 6 (2.4%) and 12 (4.1%) months. Similarly, total hip BMD declined by 0.8% at 6 months and 2.6% at 12 months. In contrast, BMD remained stable in ZA patients (P < .0001 compared with placebo).

Conclusion: Premenopausal women receiving chemotherapy for BC sustained significant bone loss at the LS and hip, whereas BMD remained stable in women who received ZA. Administration of ZA during the first year of chemotherapy is an effective and well-tolerated strategy for preventing bone loss.

Fig 1.

CONSORT diagram of patient participation and drop out throughout the study period. Drop out resulted from patients not wanting to come back for follow-up assessments. (*) Two patients on zoledronic acid (ZA) arm were excluded from analysis because bone mineral density (BMD) analysis was performed on two different dual-energy x-ray absorptiometry densitometers.

Fig 2.

Percent change in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) 24 and 52 weeks from baseline in women treated with zoledronic acid or placebo. Percent change in LS BMD in the placebo group was −3.5 and −5.6 at 24 and 52 weeks, respectively, in the subset of patients at the primary enrollment site.

Fig 3.

Mean percent change from baseline to 52 weeks in (A) bone-specific alkaline phosphatase (BSAP), a marker of bone formation, and (B) C-telopeptide of type I collagen (CTX), a marker of bone resorption. (*) P < .001 between groups. (†) P < .001 within groups.