The Role of 1,25- OH 2D3 in Bone

It is well known that vitamin D administration results in the alleviation of rickets and osteomalacia, or in biochemical terms stimulates the mineralization of organic matrix of bone and growth plate cartilage. The major defect in the mineralization of bone in vitamin D deficiency appears to be a lack of supply of calcium and phosphoras to the mineralization centers although a direct effect of some form of vita- 

Vitamin D functions in the process of calcium mobilization from previously formed bone making it available to the extracellular fluid upon demand by the calcium homeostatic system as described under the regulation of vitamin D metabolism. From the experiments described in the metabolism section it is clear that 1, 25-(0H)2D3, rather than 25-OH-D3 or vitamin D3 functions in the mobilization of calcium from bone under physiologic conditions. The mechanism whereby 1,25-(0H)2D3 initiates mobilization of calcium from bone is not at all understood. In contrast to the response of intestinal calcium transport to 1, 25-(0H)2D3 this process is blocked by the prior administration of actinomycin D suggesting that in fact a transcriptive event is involved in this activation As previously pointed out, bone possesses a specific receptor for 1,25 OH)2D3 The nature of the protein or proteins which are formed in response to 1,25 OH)2D3 in the bone cells has not yet been determined however. In vivo the 1,25-(OH)2D3 activation of bone calcium mobilization requires the presence of parathyroid hormone but the nature of 

Some attention has been focused on a possible role of vitamin D in renal reabsorption of phosphate. Although early work suggested a vitamin D stimulated increase in renal reabsorption of phosphate, this appeared the result of an ad-justment of parathyroid glands and not a direct effect of vitamin D on renal reabsorption of phosphate. More recent attempts utilizing the metabolites of vitamin D are also not convincing since vitamin D-deficient animals were not used and thus pharmacological effects of the metabolites were studied. Other reports with rats have appeared which suggest but do not prove an effect of vitamin D on the reabsorption of phosphate  

It is well known that vitamin D increases serum phosphate levels of rachitic rats which is in turn responsible for the mineralization of bone The source of the phosphate has been examined in rats on extremely low phosphorus diets so that intestinal absorption would be a minor factor The response to 1, 25 0H)2D3 was found to the same extent in these animals as in those on a 0.1% phosphorus diet. Increased renal reabsorption of phosphate was excluded by direct examination  

The animals avidly reabsorb all the phosphorus presented to the kidn even without vitamin D. The source of this phosphate proved to be bone as revealed by Ca and experiments Parathyroidectomy did not prevent the response. Thus in hypophosphatemic animals, l,25-(OH)2D3 can mobilize calcium and phosphorus from bone without parathyroid hormone. 

---