Bone loss is a frequent complication of aromatase inhibitors (AIs) therapy in women with breast cancer. Bone-active drugs are effective in protecting the skeleton from detrimental actions of AIs. However, bone mineral density (BMD) was the primary end-point in most of published studies, whereas data on fractures were scant and mainly limited to denosumab. In this prospective study, we investigated the effects of denosumab, oral bisphosphonates and intravenous zoledronate on risk of morphometric vertebral fractures (VFs; primary end-point) and BMD at lumbar spine, femoral neck and total hip (explorative end-point). To address these aims, 567 consecutive women (median age 62 years, range 28-83) were evaluated for BMD and morphometric VFs at baseline and after 18-24 months of follow-up. The inclusion criteria were: 1) hormone receptor-positive breast cancer with indication to AIs; 2) duration of AIs therapy at study entry ≤12 months. After enrolment, 268 women (47.3%) started denosumab 60 mg subcutaneously every 6 months, 59 (10.4%) oral bisphosphonates (BPs), 56 (9.9%) intravenous zoledronate 5 mg every 12 months, whereas 184 women (32.5%) were not treated with bone-active drugs because of patient preference, contraindications and/or clinical judgment. Vitamin D, with or without calcium, was given to all women during study period. Denosumab was given more frequently to women with pre-existing VFs (P=0.019) and/or lower BMD values (P<0.01 at all skeletal sites) as compared to women treated with oral BPs or zoledronate. During 18-24 months of follow-up, 54 women (9.5%) developed new morphometric VFs, with incidence being higher in untreated women vs those treated with any bone-active drug (17.4% vs 5.7%; P<0.001). Stratifying women for type of anti-osteoporotic medications, risk of VFs resulted to be significantly decreased by denosumab [odds ratio (OR) 0.22, 95% confidence interval (C.I.) 0.11-0.46; P<0.001) and zoledronate (OR 0.27, 95% C.I. 0.08-0.91; P=0.035), but not by oral BPs (OR 0.64, 95% C.I. 0.27-1.54; P=0.317). All anti-osteoporotic medications induced significant increase in median BMD at any skeletal site, whereas BMD decreased significantly in women who were not treated with bone-active drugs. In conclusion, this prospective study, reflecting the real-life clinical practice, shows that in women exposed to AI therapy, denosumab and zoledronate are more effective than oral BPs in decreasing the risk of VFs during the first 24 months of treatment. Future prospective studies will clarify whether in the long-term also oral BPs could reduce the risk of fractures in women exposed to estrogen-deprivation therapies.
21 May 2022 - 24 May 2022