What is the role of vitamin D metabolism in the pathogenesis of disorders of bone mineralization?

Updated: Jun 19, 2020
  • Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
  • Print


The primary absorption site for vitamin D is the jejunum. The 2 main sources of vitamin D in humans are vitamin D3 (cholecalciferol), produced by the skin after ultraviolet (UV) radiation (290-320nm) – dependent conversion of 7-dehydrocholesterol, and dietary intake of either vitamin D2 (ergocalciferol) or vitamin D3. Both forms of vitamin D have identical biologic actions.

The initial step in the metabolic activation process is the introduction of a hydroxyl group at the side chain at C-25 by the hepatic enzyme, CYP 27 (a vitamin D-25-hydroxylase). The products of this reaction are 25-(OH)D2 and 25-(OH)D3, respectively. Further hydroxylation of these metabolites occurs in the mitochondria of kidney tissue, catalyzed by renal 25-hydroxyvitamin D-1α-hydroxylase to produce 1α,25-(OH)2 D2 (activated vitamin D2 or 1,25[OH]2 D2), the primary biologically active form of vitamin D2, and 1α,25-(OH)2 D3 (calcitriol or 1,25[OH]2 D3), the biologically active form of vitamin D3.

Of note, the kidney generates at least 30 other vitamin D metabolites, but their biologic significance is not clear. The pathophysiology of rickets is not completely understood, nor is the role of the many vitamin D metabolites. Calcitriol levels may be normal in patients with rickets, suggesting that it is not the only active form of the vitamin.

Causes of rickets related to phosphate deficiency are discussed in the article Hypophosphatemic Rickets.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!