Background: Women with primary breast cancer who receive systemic therapy may experience ovarian failure or early menopause, leading to a loss of bone mineral density (BMD). Loss of BMD may be reduced by use of bisphosphonates, compounds that inhibit the action of osteoclasts (cells that absorb or remove bone tissue). We have conducted a double-blind, randomized, two-center trial to evaluate BMD in women with primary breast cancer who were given the bisphosphonate clodronate (1600 mg/day orally) or placebo for 2 years.
Methods: From August 31, 1990, through March 31, 1996, more than 300 eligible patients had been accrued, randomly assigned to study treatment, given the appropriate primary surgical care and systemic (chemotherapy and/or tamoxifen) therapy, and had completed follow-up for at least 1 year. BMD in the lumbar spine and in the hip, including the trochanteric area, was measured by use of dual-energy x-ray absorptiometry at the beginning of treatment and after 1 and 2 years of treatment. Changes in BMD were calculated as percent changes from the initial readings. Treatment effects for clodronate versus placebo (i.e., mean percent changes in BMD with clodronate minus mean percent changes in BMD with placebo) at 1 and 2 years for individual sites were calculated.
Results: After 1 year, the treatment effects for clodronate versus placebo in the lumbar spine, the total hip, and the trochanter, respectively, were as follows: +2.38% (95% confidence interval [CI] = 1.36-3.41), +0.74% (95% CI = -0.13 - 1.60), and +1.29% (95% CI = 0.24-2.34). After 2 years, the corresponding treatment effects were +1.72% (95% CI = 0.12-3.34), +1.85% (95% CI = 0.51-3.20), and +2.30% (95% CI = 0.66-3.94), respectively.
Conclusions: Oral clodronate appears to reduce the loss of BMD in patients who receive treatment for primary breast cancer.