The vitamin D receptor gene and calcium metabolism

Dietary Ca2+ is essential for the development and maintenance of bone mineral mass. The vitamin D endocrine system plays a fundamental role in the regulation of Ca2+ homeostasis, and mutations affecting genes implicated in vitamin D metabolism or vitamin D receptor (VDR) functions ave 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 oft he 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 Ca2+ and phosphate metabolism, except perhaps VDR 3'-end polymorphisms before puberty. As these associations ave so inconsistent, interactions with environmental factors, particularly dietary intake, and with other polymorphisms have to be considered.