Tamoxifen has been clinically used in ERα-positive breast cancers as an antagonist of estrogen signaling in mammary epithelial cells; simultaneously, it elicits secondary ERα-agonist effects in bone, preventing osteoporosis, but also acts as an agonist in the uterus, leading to an increased risk of endometrial cancer (Braun et al., 2016; Rachner et al., 2018; Emons et al., 2020). This evidence concerns the gene ESR1 and osteoporosis.