Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials

Aromatase inhibitors (AIs) are routinely used to treat postmenopausal women with early-stage breast cancer. Although AIs improve breast cancer outcomes, they increase the risk of osteoporosis and fractures. This systematic review and meta-analysis assesses the effect of antiresorptive drugs on AI induced bone loss in postmenopausal women with non-metastatic breast cancer.We searched four databases until November 4th 2020. We included Randomized controlled trials (RCTs) of antiresorptive drugs in postmenopausal women with breast cancer treated with AI. Two authors screened studies, extracted data and assessed the risk of bias independently and in duplicate.We identified 14 RCTs: 7 on zoledronic acid, 6 on oral bisphosphonates and 1 on denosumab. The mean difference in bone mineral density (BMD) was 5% at the lumbar spine and 4% at the total hip, at 12 months, favoring zoledronic acid compared to control. The certainty of the evidence was low for lumbar spine and moderate for total hip BMD. Similarly, the mean difference was 3% at the lumbar spine and 2% at the total hip, favoring oral bisphosphonates with moderate certainty. The mean difference was 6% at the lumbar spine, and 4% at the total hip BMD favoring denosumab compared to placebo. In addition, zoledronic acid resulted in a mean difference in bone turnover marker levels of -35-41%, and the relarive risk for morphometric vertebral fractures was 0.7 [0.3-1.4], compared to control. Denosumab reduced fracture incidence by 50% compared to placebo.Evidence suggests a protective effect of antiresorptive drugs on BMD and bone turnover markers in postmenopausal women with non-metastatic breast cancer on AI. However, data on fracture risk reduction remains unclear.