25(OH)D is the major circulating form of vitamin D, with a circulating half-life of 2–3 weeks. It is the best indicator to monitor for vitamin D status.1
The circulating half-life of 1,25(OH)2D, on the other hand, is approximately 4 hours. It circulates at a 1,000-times lower concentration than 25(OH)D, and the blood level is tightly regulated by serum levels of PTH, calcium, and phosphate. Serum 1,25(OH)2D does not reflect vitamin D reserves, and measurement of 1,25(OH)2D is not useful to monitor vitamin D status. Serum 1,25(OH)2D is frequently either normal or even elevated in those with vitamin D deficiency, because of secondary hyperparathyroidism. Thus, 1,25(OH)2D measurement does not reflect vitamin D status.1
Measurement of 1,25(OH)2D is useful only for patients with disorders of 25(OH)D and phosphate metabolism. These include chronic kidney disease, hereditary phosphate-losing disorders, oncogenic osteomalacia, pseudovitamin D-deficiency rickets, vitamin D-resistant rickets, and chronic granuloma-forming disorders, such as sarcoidosis and some lymphomas.1