Methods and compositions for treating 25-hydroxyvitamin D insufficiency or deficiency in a patient are described herein. The method includes orally administering to the patient a sustained release formulation of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3. The 25-hydroxyvitamin D is administered in combination with one or more agents selected from: one or more calcium salts, bisphosphonates, calcimimetics, nicotinic acid, iron, phosphate binders, glycemic control agents, hypertension control agents, and antineoplastic agents.