Methods of treating vitamin D-sensitive diseases without inducing severe forms of hypercalcemia. The methods comprise administering biologically inert vitamin D prodrugs. The vitamin D prodrugs have a vitamin D-drug moiety and a pro moiety, wherein the pro moiety is selected from the group consisting of a glycone moiety and a sulfate moiety. The vitamin D prodrugs are activated by enzymes at target tissues or cells that cleave the pro moiety from the vitamin D drug moiety, freeing the vitamin D-moiety from the pro moiety in the vicinity of the target tissues or cells. The methods of the invention prevent large, acute, systemic increases in the free form of the vitamin D-drug moiety that would otherwise lead to hypercalcemia. The methods can be used to treat hyperproliferative, autoimmune, or infectious diseases throughout the body, including the intestine. Compositions of the vitamin D prodrugs useful in the described methods are also disclosed.
