Herein, our data showed that the aberrant activation of the Nlrp3‐mediated pyroptosis of osteoblasts within the vertebral bodies of STZ‐induced DM rats was accompanied by impaired osteogenic differentiation (evidenced by decreased levels of Runx2 and Osterix) and secretory capacity (evidenced by reduced Opg, Oc and Col1). Here, RUNX2 is linked to diabetes mellitus.