Osteoporosis, a common skeletal disease is featured by systemic impairment of bone mass, strength, and microarchitecture, which increases the risk for fragility fractures.208 Oxygen is required for the activity of skeletogenic cells and many fundamental cellular processes that are critical for normal fracture healing.209 In recent years, several studies elucidated the mechanisms by which HIFs (HIF-1α and HIF-2α) impact bone remodeling and pathologies.210 However, the underlying correlations between hypoxia signaling and osteoporosis remain poorly understood. Here, EPAS1 is linked to osteoporosis.