ORAL CLODRONATE AND REDUCTION IN LOSS OF BONE-MINERAL DENSITY IN WOMEN WITH OPERABLE PRIMARY BREAST-CANCER

Background: Women with primary breast cancer who receive systemic ther apy may experience ovarian failure or early menopause, leading to a lo ss of bone mineral density (BMD), Loss of BMD may be reduced by use of bisphosphonates, compounds that inhibit the action of osteoclasts (ce lls that absorb or remove bone tissue). We have conducted a double-bli nd, randomized, two-center trial to evaluate BMD in women with primary breast cancer who were given the bisphosphonate clodronate (1600 mg/d ay orally) or placebo for 2 years. Methods: From August 31, 1990, thro ugh March 31, 1996, more than 300 eligible patients had been accrued, randomly assigned to study treatment, given the appropriate primary su rgical care and systemic (chemotherapy and/or tamoxifen) therapy, and had completed follow-up for at least 1 year. BMD in the lumbar spine a nd in the hip, including the trochanteric area, was measured by use of dual-energy x-ray absorptiometry at the beginning of treatment and af ter 1 and 2 years of treatment. Changes in BMD were calculated as perc ent changes from the initial readings. Treatment effects for clodronat e versus placebo (i.e., mean percent changes in BMD with clodronate mi nus mean percent changes in BMD with placebo) at 1 and 2 years for ind ividual sites were calculated. Results: After 1 year, the treatment ef fects for clodronate versus placebo in the lumbar spine, the total hip , and the trochanter, respectively, were as follows: +2.38% (95% confi dence 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 clod ronate appears to reduce the loss of BMD in patients who receive treat ment for primary breast cancer.