In summary, we indicate that defective osteogenic differentiation of Zmpste24−/− BMMSCs can be partly attributed to the inhibition of canonical Wnt pathway which is partly owing to decreased Cav1.2 expression, and Bay K8644 treatment could be an applicable approach for treating age‐related bone loss by ameliorating compromised osteogenic differentiation capacity through targeting Cav1.2 channel and canonical Wnt pathway. Here, CACNA1C is linked to age.