Notably, the EVs collected from the serum of patients during denosumab treatment had reduced ability to stimulate osteoclastogenesis compared to EVs collected from treatment-naïve patients with osteoporosis (Fig. 7f), suggesting that the RANKL expressed on EVs did not have a stimulatory role due to a masking effect of denosumab. This evidence concerns the gene TNFSF11 and osteoporosis.