These signatures converge on pathways associated with the increase of osteoclast function, such as the RANKL pathway, shared by EVs circulating in both models of osteoporosis, but diverge in pathways, such as Leptin, Lipocalin 2 and Osteopontin, whose modulations are consistent with impairment of osteoblast function and are apparently more prominent in HL-TS, likely disturbing the balance of the bone multicellular unit in a manner different from OVX. The gene discussed is SPP1; the disease is osteoporosis.