(13-01-10) Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

M Peterlik1 and H S Cross1
1Department of Pathophysiology, University of Medicine Vienna, Vienna, Austria
Correspondence: Professor M Peterlik, Department of Pathophysiology, Medical University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: [email protected]
Received 10 February 2009; Revised 16 July 2009; Accepted 20 July 2009; Published online 2 September 2009.
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Abstract
A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1 -hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and extracellular Ca2+ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)2D3-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

Source: European Journal of Clinical Nutrition (2009) 63, 1377?1386

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