Vitamin D and bone

AbstractIt is now well established that supraphysiological doses of 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3] stimulate bone resorption. Recent studies have established that osteoblasts/stromal cells express receptor activator of NF‐κB ligand (RANKL) in response to several bone‐resorbing factors including 1α,25(OH)2D3 to support osteoclast differentiation from their precursors. Osteoclast precursors which express receptor activator of NF‐κB (RANK) recognize RANKL through cell‐to‐cell interaction with osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of macrophage‐colony stimulating factor (M‐CSF). Osteoprotegerin (OPG) acts as a decoy receptor for RANKL. We also found that daily oral administration of 1α,25(OH)2D3 for 14 days to normocalcemic thyroparathyroidectomized (TPTX) rats constantly infused with parathyroid hormone (PTH) inhibited the PTH‐induced expression of RANKL and cathepsin K mRNA in bone. The inhibitory effect of 1α,25(OH)2D3 on the PTH‐induced expression of RANKL mRNA occurred only with physiological doses of the vitamin. Supraphysiological doses of 1α,25(OH)2D3 increased serum Ca and expression of RANKL in vivo in the presence of PTH. These results suggest that the bone‐resorbing activity of vitamin D does not occur at physiological dose levels in vivo. A certain range of physiological doses of 1α,25(OH)2D3 rather suppress the PTH‐induced bone resorption in vivo, supporting the concept that 1α,25(OH)2D3 or its derivatives are useful for the treatment of various metabolic bone diseases such as osteoporosis and secondary hyperparathyroidism. J. Cell. Biochem. 88: 259–266, 2003. © 2002 Wiley‐Liss, Inc.