Physiological functions of vitamin D: what we have learned from global and conditional VDR knockout mouse studies

•The physiological role of vitamin D depends on calcium supply and calcium balance.•When the calcium balance is normal, the major target of vitamin D is intestine.•Vitamin D stimulates mainly active intestinal calcium transport mechanism.•During a negative calcium balance, bone effects of vitamin D become dominant.•The role of vitamin D in maintaining normocalcemia has priority over skeletal integrity.

The physiological role of vitamin D depends on calcium supply and calcium balance. When the calcium balance is normal, the major target of vitamin D is intestine. Vitamin D stimulates mainly active intestinal calcium transport mechanism. During a negative calcium balance, bone effects of vitamin D become dominant. Thus, the role of vitamin D in maintaining normocalcemia appears to have priority over skeletal integrity in these situations.