Our results firstly demonstrated that SPTBN1 could efficiently prevent the progression of primary osteoporosis through facilitating the proliferation and differentiation of osteoblast, inhibiting apoptosis of osteoblast via regulating TGF-β/Smad3, STAT1/Cxcl9 pathways, and promoting the formation of blood vessels in bone by modulating VEGF expression. Here, VEGFA is linked to osteoporosis.