Excerpt
Vitamin D was originally identified as a factor which cured rickets in children and osteomalacia in adults. It was misnamed, since it is not an essential dietary constituent, but a hormonal precursor made in the skin following exposure to ultraviolet light. It plays a pivotal role in bone health, and the osteomalacia seen in vitamin D-deficient humans is recapitulated in animals lacking the vitamin D receptor (VDR). The VDR is present in bone cells, in the gut, and in a number of other tissues, though there is ongoing controversy with respect to its expression in muscle [
1]. Elegant experiments have demonstrated that the osteomalacia of the VDR knockout mouse can be completely corrected by the selective expression of VDR in the enterocytes of the gut [
2]. Conversely, selective knockout of the VDR in the gut reproduces the osteomalacic phenotype, indicating that it is the effect of VDR to facilitate calcium absorption that is critical to its effect on bone health [
3]. In fact, selective knockout of VDR from bone is associated with an increase in bone mass, suggesting that the direct effects of the vitamin D endocrine system on bone are negative [
3,
4]. The direct actions of VDR on bone are mediated via the osteoblast, and result in increased expression of the osteoclastogenic factor, RANKL, and suppression of its antagonist, osteoprotegerin. There is also recent evidence that activation of VDR in bone increases bone pyrophosphate levels, resulting in decreased bone mineralisation [
3]. These findings clarify the biological role of VDR, which is primarily to maintain extracellular fluid calcium concentrations, rather than to maintain bone health. In times of calcium privation, the vitamin D/endocrine system will deplete the skeleton of calcium, such that serum calcium can be maintained, since this is critical to the normal function of the nervous system, the heart, muscle and blood coagulation. Thus, vitamin D is not a tonic for bone, but its adequate provision is necessary for bone health [
5]. …
