Originally published as JCO Early Release 10.1200/JCO.2008.16.4707 on August 18 2008

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Zoledronic Acid Prevents Bone Loss in Premenopausal Women Undergoing Adjuvant Chemotherapy for Early-Stage Breast Cancer

Dawn L. Hershman, Donald J. McMahon, Katherine D. Crew, Serge Cremers, Dinaz Irani, Gina Cucchiara, Lois Brafman, Elizabeth Shane

From the Department of Medicine; Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons; and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY

Corresponding author: Dawn L. Hershman, MD, MS, Columbia University, 161 Fort Washington Ave, 10-1068, New York, NY 10032; e-mail: dlh23{at}columbia.edu

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.

published online ahead of print at www.jco.org on August 18, 2008

Supported by a K07 Award from the National Cancer Institute (Grant No. CA95597) (D.L.H.), a career development award from American Society of Clinical Oncology (D.L.H.), a K24 Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 052665) (E.S.), and Novartis Pharmaceuticals Corporation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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