Abstract With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi‐1 co‐localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1 ‐driven Bmi‐1 knockout in bone‐marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation…