CYP27A1 and osteoporosis: Though there are some proteins secreted by the liver that involve bone metabolism13, alterations of VitD metabolism is the most studied liver–bone communication contributor to primary osteoporosis, as VitD is hydroxylated by VitD 25-hydroxylase (CYP2R1) and sterol 27-hydroxylase (CYP27A1) in the liver12; however, VitD supplementation alone is not sufficient to prevent or delay loss of bone mineral density (BMD) in patients with osteoporosis.