ACE2 and osteogenesis imperfecta: Additionally, ACE2 expression tends to decrease with age, and its activity is lower in males than in females (likely due to estrogen upregulating ACE2 expression and the fact that ACE2 is located on the X chromosome), which may help explain why children with osteogenesis imperfecta (OI) tend to be older, and why the prevalence of the condition is higher in females compared to males (34, 35).