10-year follow-up of the efficacy of clodronate on bone mineral density (BMD) in early stage breast cancer

Abstract

676 Background: We have previously reported that clodronate prevents bone loss in breast cancer patients (JCO 1997;15:1341, BJC 1997;75(4):602 and EJC 2001;37:2373). Here we report the 10-year follow-up data. Methods: 268 pre- (PRE) and postmenopausal (POST) node positive breast cancer patients were randomized to clodronate (CL), orally 1.6 g daily, or control groups for 3 years. PRE were treated with adjuvant chemotherapy and POST with antiestrogens (AE), tamoxifen 20 mg or toremifene 60 mg, for 3 years. The BMD of the lumbar vertebrae L1–4 (BMDLS) and femoral neck (BMDFN) was measured before the treatment and at 1, 2, 3, 5 and 10 years. 93 patients were eligible for 10-year analyses: 53 PRE and 40 POST. 132 patients had metastatic disease or died and 39 were either lost to follow-up or had to be excluded because having diseases or medications that influences bone metabolism. Results: PRE: BMDLS decreased -12.4% in the control and −8.7% in the CL group in 10 years: from 0 to 3 years −6.9 % vs. −4.2% and from 3 to 10 years −5.5% and −4.5%, respectively. BMDFN decreased −8.8% and −7.2%: from 0 to 3 years −2.9% vs. −2.6% and from 3 to 10 years −5.9% vs. −4.6%, respectively. POST: BMDLS decreased −3.0% in the AE and −1.7% in the AE+CL group in 10 years: from 0 to 3 years −1.5% vs. + 1.2% and from 3 to 10 years −1.5% vs. −2.9%, respectively. BMDFN decreased −7.7% and −6.0%: from 0 to 3 years −0.1% vs. +1.9% and from 3 to 10 years −7.6% vs. −7.9%, respectively. These differences do not reach statistical significance. At 10-years 18 patients had osteoporosis in LS and 15 in FN. Only 4 patients who had osteoporosis at 10 years had normal BMD before the therapy. Conclusions: As reported previously, clodronate prevents the bone loss during treatment in pre- and postmenopausal women. This beneficial effect seems to be maintained at least for 7 years after treatment termination in premenopausal. In postmenopausal women the effect seems to diminish within time. Due to small numbers of patients these differences are no longer statistically significant. Patients at risk of developing osteoporosis are among those who has pretreatment osteopenia i.e. baseline BMD measurement has predictive value. No significant financial relationships to disclose.