There may be a causal relationship between 25 plasma protein markers and osteoporosis, among which serine/threonine-protein kinase pim-1, ATP1B1, ZFP175, and chordin-like protein 2 may significantly increase the risk of osteoporosis, while ANKED46, KLRF1, LPO, and CA9 may significantly reduce the risk of osteoporosis. This evidence concerns the gene KLRF1 and osteoporosis.