Novel Targets of Vitamin D Activity in Bone: Action of the Vitamin D Receptor in Osteoblasts, Osteocytes and Osteoclasts

The active form of vitamin D, 1,25-dihydroxyvitamin D3, carries out its diverse range of biological activities by binding to the nuclear vitamin D receptor, present in almost every cell of the body. It is well established that adequate serum 25-hydroxyvitamin D levels correlate with a reduction in the incidence of osteoporosis; however, the physiological basis for this relationship remains elusive. Although, the endocrine actions of vitamin D are thoroughly appreciated, the effect of vitamin D on bone tissue and bone cells is yet to be completely understood. There exists a wealth of literature that suggests the VDR within the three major bone cell types, osteoblasts, osteocytes and osteoclasts, is responsible for the regulation of bone homeostasis. The circumstances, under which the action of 1,25-dihydroxyvitamin D3 elicits an anabolic or catabolic role have not been elucidated. However, it would seem that vitamin D can evoke both of these effects and that this is partly mediated by calcium homeostasis. This raises the possibility that dietary calcium intake and vitamin D metabolism act concomitantly at the kidney, intestine and the bone in a coordinated response. Thus, to maintain adequate bone homeostasis and reduce the risk of metabolic bone disease via the diet, it is important to consider this duality of vitamin D action in relation to the overall calcium economy.