The vitamin d receptor gene and calcium metabolism

Dietary Ca(2+) is essential for the development and maintenance of bone mineral mass. The vitamin D endocrine system plays a fundamental role in the regulation of Ca(2+) homeostasis, and mutations affecting genes implicated in vitamin D metabolism or vitamin D receptor (VDR) functions are responsible for severe alterations in skeletal growth. In addition, vitamin D is also implicated in the pathophysiology and treatment of adult bone disorders associated with impaired mineralization of bone matrix. Very recently, common polymorphisms in the 3'- and 5'-end region of the VDR gene have been suggested as possible determinants of bone mineral mass and, hence, of the risk of osteoporosis. None of these polymorphisms appear to be associated unequivocally with bone mineral mass or biochemical variables of Ca(2+) and phosphate metabolism, except perhaps VDR 3'-end polymorphisms before puberty. As these associations are so inconsistent, interactions with environmental factors, particularly dietary intake, and with other polymorphisms have to be considered.