Prevention of breast cancer treatment-induced bone loss in premenopausal women treated with zoledronic acid: Final 5-year results from the randomized, double-blind, placebo-controlled ProBONE II trial.

Purpose: Premenopausal women receiving chemotherapy or endocrine treatment for early breast cancer are at increased risk for cancer treatment induced bone loss (CTIBL). The aim of the randomized, double-blind ProBONE II trial was to investigate whether a 2-year adjuvant treatment with 4 mg intravenous zoledronic acid (ZOL) every 3 months versus placebo would prevent CTIBL after a five-year period.

Methods: Thirty-one of the 34 participants in the ZOL arm and thirty-four of the 36 participants in the placebo arm were followed-up to the 5-year visit and completed the study as planned. The changes in Bone Mass Density (BMD) were assessed at baseline and each visit after treatment initiation.

Results: After 24 months, BMD at the lumbar spine showed a 2.9% increase in patients treated with ZOL vs. a 7.1% decrease in placebo-treated participants compared to baseline (p < 0.001). Over the 60-month study period, we found a decrease of 2.2% vs. 7.3% in the BMD at the lumbar spine in patients receiving ZOL and placebo respectively (p < 0.001). Over the 60-month study period, BMD in the placebo arm showed a continuous decrease at all sites (p < 0001), whereas patients treated with ZOL reached baseline BMD-values at the femoral neck and total hip.

Conclusions: In ProBone II, a 2-year treatment with ZOL 4 mg intravenous every 3 months prevented cancer treatment induced bone loss in premenopausal women with breast cancer and maintained the BMD up to 3 years post-treatment.