Efficacy of zoledronic acid for prevention of bone loss in early-stage breast cancer patients receiving adjuvant therapy: A meta-analysis of 13 randomized controlled trials

Abstract

Early-stage breast cancer (BC) patients receiving adjuvant therapy suffer from bone loss and increased fracture risk. Zoledronic acid (ZA) has been confirmed to inhibit bone metastasis and improve survival outcomes in early BC postmenopausal patients receiving adjuvant therapy. However, the efficacy of ZA for prevention of adjuvant therapy-induced bone loss from 2 different early BC groups, namely premenopausal and postmenopausal patients, still remain unclear. To obtain detailed characteristics, we performed this meta-analysis. PubMed, EMBASE, and Cochrane were searched. In premenopausal BC patients and postmenopausal BC patients, to assess bone loss, we calculated the weighted mean differences with 95% confidence intervals (CI) to evaluate lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and femoral neck (FN) BMD in ZA and non-ZA group with follow-up of 12 months. Thirteen randomized controlled trials (RCTs) encompassing 7375 patients were included. In a mixed population of early BC patients receiving adjuvant therapy, ZA significantly increased LS BMD (P < 0.00001), TH BMD (P < 0.00001), and FN BMD (P = 0.01) compared with non-ZA group. In premenopausal patient subgroup, LS BMD was greatly higher in patients with ZA compared to controls (0.06 g/cm²; 95% CI: 0.05-0.08), whereas there were no differences in TH BMD and FN BMD between patients with ZA and controls. In postmenopausal patient subgroup, both LS BMD (0.06 g/cm²; 95% CI: 0.05-0.07) and TH BMD (0.04 g/cm²; 95% CI: 0.03-0.04) were significantly higher in patients with ZA compared to controls, but there was no difference in FN BMD between patients with ZA and controls. To sum up, ZA prevents bone loss in early-stage BC patients receiving adjuvant therapy at different skeletal sites. In premenopausal patients, effectiveness of ZA in prevention of bone loss is confirmed at LS site, but not at TH and FN site. In postmenopausal patients, ZA has a satisfying efficacy for prevention of bone loss at LS and TH site, but not at FN site.

Keywords: Adjuvant therapy; Bone mineral density; Early-stage breast cancer; Meta-analysis; Randomized controlled trials; Zoledronic acid.