Benefit of zoledronic acid during chemotherapy persists after discontinuation

NEW YORK (Reuters Health) - Zoledronic acid prevents chemotherapy-related bone loss in premenopausal breast cancer patients for up to a year after it's discontinued, according to a post hoc analysis of a randomized trial.

In the primary analysis, reported in 2008, Dr. Dawn L. Hershman and colleagues at Columbia University in New York found that treatment for 1 year with zoledronic acid prevented significant bone loss at all sites in these women. In their secondary analysis, they wanted to see what effect, if any, the 12 months of treatment would have on bone mineral density (BMD) and bone turnover markers during the year after the last administered dose.

In fact, the year of treatment with zoledronic acid actually produced a slight increase in BMD, and although the women in the treatment group had a nonsignificant decrease in BMD over the next 12 months, the researchers describe the reduction as a "return to baseline."

In the February 2010 issue of the Journal of Clinical Endocrinology and Metabolism, posted online December 18th, the authors report that 101 premenopausal women undergoing chemotherapy for nonmetastatic breast cancer had been randomized to receive either zoledronic acid (4 mg IV every 3 months for 1 year) or placebo. Eight-five and 62 women completed evaluations at 12 and 24 months, respectively.

Women given placebo had significant bone loss during their year of chemotherapy, without recovery during the second year, the investigators said. Lumbar spine BMD decreased from baseline by 5.4% at 12 months and 6.3% at 24 months in the placebo arm. By 24 months, total hip and femoral neck BMD had decreased by 2.6% and 2.4%, respectively.

In contrast, in women treated with zoledronic acid for 1 year, BMD increased slightly at each site at 12 months and then remained stable.

Bone-specific alkaline phosphatase (BSAP), a serum marker of bone formation, and serum C-telopeptide of type I collagen (CTX), a marker of bone resorption, "increased progressively and significantly during the first year" in the placebo group, the authors said. Serum CTX declined during the second year, but both markers were significantly above baseline at 12 and 24 months.

In the zoledronic acid arm, serum BSAP and CTX declined significantly by 6 months, but returned to baseline by 12 months. One year later, however, serum BSAP was significantly above baseline, and CTX was similar to levels in the placebo group.

These observations, the researchers note, suggest that more frequent administration of zoledronic acid may be needed to suppress bone resorption.

Dr. Hershman received research support for the study from the National Cancer Institute and the American Society of Clinical Oncology. Additional support for the study was provided by Novartis Pharmaceuticals Corporation, which markets zoledronic acid under the trade name Zometa.

Copyright © 2010 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.