73P Change in the bone absorption marker levels in aromatase inhibitor-treated patients who were switched from oral bisphosphonates to denosumab

Abstract

Background: Aromatase inhibitors (AIs) are known to increase the risk of fractures and reduce bone mineral density in postmenopausal patients with estrogen receptor (ER)-positive breast cancer. The ABCSG-18 trial demonstrated that denosumab significantly increased bone mineral density in patients with non-metastatic breast cancer who were receiving AIs. However, the effect of denosumab in patients who have received treatment with oral bisphosphonates for the prevention of bone loss and factures is still unknown. Methods: Between January 2015 and January 2016, we enrolled 21 postmenopausal patients with ER-positive breast cancer. Of these patients, 10 were switched from oral bisphosphonates to denosumab (switch group) and 11 were treated with denosumab for the first time (initial group). The mean age was 74 years (range, 61-84 years) in the convert group and 71 years (range, 58-83 years) in the initial group. The mean T-scores for the lumbar spine and femoral neck, assessed by using dual-energy radiographic absorptiometry, were respectively ≥2.9 (range, 1.8 to≥3.9) and ≥2.5 (range, ≥2.0 to≥4.2) in the switch group, and ≥2.0 (range, 0.6 to≥3.5) and ≥2.3 (range,≥1.3 to≥2.8) in the initial group. All the patients concurrently received vitamin D2 (ergocalciferol) supplementation with AIs. The percent change in urine N-telopeptide crosslinked type 1 collagen (u-NTx) level was measured at baseline and after 1 month of denosumab therapy. Results: In the switch group, 8 of 10 patients had a decreased change in u-NTX level, which was above the maximumsignificant change (27.3%). The mean percentage change in u-NTX level was 54.1% (95% confidence interval [CI], 40.3-67.9%). On the other hand, 10 of 11 patients in the initial group had a decreased change, with a mean percentage change in u-NTX level of 60.0% (95% CI, 42.7-77.2%). None of the patients had adverse reactions, including hypocalcemia, backache, and arthralgia. Conclusions: After switching oral bisphosphonates to denosumab, the mean percent change in u-NTX level was similar to that in the initial use of denosumab. We suggest that clinicians should switch oral bisphosphonates to denosumab for the prevention of AI-induced bone loss and fractures.