Abstract
It is now well established that supraphysiological doses of 1α,25‐dihydroxyvitamin D~3~ [1α,25(OH)~2~D~3~] 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)~2~D~3~ 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)~2~D~3~ 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)~2~D~3~ on the PTH‐induced expression of RANKL mRNA occurred only with physiological doses of the vitamin. Supraphysiological doses of 1α,25(OH)~2~D~3~ 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)~2~D~3~ rather suppress the PTH‐induced bone resorption in vivo, supporting the concept that 1α,25(OH)~2~D~3~ 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.