In contrast, Pitx1 overexpression induced osteoporosis by repressing Runx2, ALP, osterix, and OCN while increasing Wnt inhibitors (Sost, Dkk1); lithium chloride partly reversed this, showing how Wnt reactivation may counter senescence-driven bone loss (Karam et al., 2019). Here, PITX1 is linked to osteoporosis.