Concomitant treatment with the bisphosphonate zoledronic acid prevents the bone loss associated with endocrine therapy for early-stage breast cancer, investigators say.

Concomitant treatment with the bisphosphonate zoledronic acid prevents the bone loss associated with adjuvant endocrine therapy for early-stage breast cancer in premenopausal women, investigators report in the September issue of The Lancet Oncology.

The findings are from a substudy of the Austrian Breast and Colorectal Cancer Study Group trial-12, a phase III trial to assess the efficacy of goserelin-induced ovarian suppression plus tamoxifen or anastrozole, with or without zoledronic acid in premenopausal women with early-stage, hormone-receptor-positive breast cancer.

Earlier this year, Dr. Michael Gnant and colleagues announced that addition of zoledronic acid to the treatment regimens substantially reduced cancer relapse and metastasis after three years of treatment and two additional years of follow-up.

The current prospective substudy included 199 women randomly assigned to endocrine therapy alone and 205 assigned to endocrine therapy plus zoledronic acid, 4 mg intravenously every six months for three years.

At 36 months, bone mineral density (BMD) at the lumbar spine remained stable in the zoledronic acid group (+0.4 per cent), but decreased significantly from baseline in the no-zoledronic acid group (-11.3per cent, p < 0.0001).

At 60 months (two years after the end of treatment), BMD had increased substantially in the zoledronate group (+4.0 per cent, p = 0.022). By contrast, women who did not receive zoledronic acid had incomplete recovery of BMD, with values still below baseline (-6.3 per cent, p = 0.001).

Bone loss in premenopausal women "is of substantial clinical concern," Dr. Gnant, at the Medical University of Vienna, and his colleagues note. "Large, population-based studies have shown that any premature decrease in BMD puts women at a distinct disadvantage as they age and increases fracture risk compared with their age-matched peers."

The risk is likely to be compounded, the authors add, since many of these patients are likely to enter premature menopause.

They plan "to monitor the long-term proportion of fractures in these two groups to establish whether substantial fracture prevention is associated with zoledronic-acid therapy."

Lancet Oncol 2008;9:840-849