Eldecalcitol Add-On to Risedronate Reduces Bone Loss from Aromatase Inhibitors in Postmenopausal Breast Cancer Patients.

Context: Aromatase inhibitors (AIs) cause bone loss and increase fracture risk in women with hormone receptor-positive early-stage breast cancer (HR+EBC). Bone antiresorptive agents are recommended for patients at risk of fragility fractures. Eldecalcitol, combined with bisphosphonate, increases bone mineral density (BMD) in primary osteoporosis.

Objective: To determine the effect of eldecalcitol (0.75 ug/day) add-on therapy to risedronate (17.5 mg/week) on bone quantity and quality in women treated with AI.

Design: Open-label randomized control trial.

Setting: Postmenopausal women with HR+EBC (TNM stage 0-3A) treated with risedronate for more than 12 months.

Patients: 200 patients were enrolled; 196 patients were eligible for the full analysis set after excluding those without follow-up BMD data. Participants were advised to take vitamin D and calcium, yet many were vitamin D deficient or insufficient.

Intervention: Participants were randomly assigned in a 1:1 ratio to receive either eldecalcitol add-on therapy or risedronate monotherapy.

Main Outcome Measure: Primary outcome was the group difference in the change of LS-BMD in 24 months. Secondary outcomes included FN-BMD, TH-BMD, trabecular bone score (TBS), and the incidence of vertebral and non-vertebral fractures.

Results: The increase at LS-, FN-, and TH-BMD at 24 months was larger in the add-on therapy group than in the monotherapy group, with a group difference (add-on therapy minus monotherapy) estimate of 0.020 g/cm2 (95% confidence interval (CI): 0.010-0.029 g/cm2, p< 0.001) for LS-BMD. The incidence rate ratio (add-on therapy/monotherapy) for morphometric vertebral fractures was 0.292 (95% CI: 0.080-1.061, p= 0.061). No group difference was detected in the change in TBS.

Conclusions: Eldecalcitol add-on therapy increased LS-BMD in osteopenic to osteoporotic postmenopausal women treated with an AI and risedronate.