Glucocorticoid (GC) associated osteoporosis is common but GC-triggered bone loss remains largely unclear. Accounting for 90% of cell population, osteocytes and their network may play critical role in response to GC administration. Previous we showed that endoplasmic reticulum (ER) regulated activity and transfer of mitochondria within osteocyte dendritic processes is critical for bone hemostasis. Here we showed for the first time that GC inhibits osteocyte hemostasis by suppressing mitochondrial transfer between osteocytes and induced secretion of cathepsin K through the induction of mitophagy of osteocytes. We first showed that dexamethasone (Dex) modified the configuration of ER in osteocytes from a tubular-like form to a stressed condensed sheet-like pattern. The change of configuration lead to the arrest of MitoTracker® Green labelled mitochondrial movement along the dendritic network and compromise mitochondrial transfer within the osteocyte dendritic network. Degradation of Mfn2 by GC induced PINK1 activation is responsible for the inhibition of mitochondrial transfer evidenced by siRNA study in MLO-Y4 cells. We further showed that PINK1-mediated mitophagy has resulted in the induction of cathepsin K in mouse calvaria culture. Knocking down PINK1 gene abolished the GC-triggered cathepsin K production, and this GC activation effects towards cathepsin K was not impeded when inhibiting the canonical autophagy via Atg5 suppression, suggesting that a non-canonical autophagy pathway promotes the production of cathepsin K in osteocytes following GC treatment. In summary, our results indicate the novel finding that GC-induced PINK1 modulates both of the mitochondrial transfer, and the production of cathepsin K in osteocytes, thereby contributing to the GC-induced bone loss.