Vitamin D and bone

Recent studies of the effects of vitamin D on bone include characterization of the receptors for 1,25-(OH)₂D₃ in bone and bone derived cells. The receptors show similar affinities in the different tissues. The receptor concentration is affected by the stage of the cell cycle. Glucocorticoid treatment affects the number of receptor sites. The most extensively studied effects of 1,25-(OH)₂D₃ on macromolecular synthesis in bone have been on collagen, where both anabolic and antianabolic effects are found. Differences in the response may reflect the state of differentiation of the cells. Significant effects are seen on osteocalcin synthesis, although the role of this protein in vitamin D action on bone is still unclear. 1,25-(OH)₂D₃ influences the activity of alkaline phosphatase and 25-OH-D₃ 24-hydroxylase in bone. Receptors for growth factors, and production of cytokines may be influenced by 1,25-(OH)₂D₃ treatment. Although some of these findings would be consistent with direct anabolic effects of vitamin D or its metabolites on bone, such a process has yet to be integrated into the complete picture of vitamin D action at physiological and pharmacological levels in vivo. Recent studies are consistent with earlier results that indicate that the hypercalcemic effects of 1,25-(OH)₂D₃ are mediated by a direct effect on bone. Studies with analogs of 1,25-(OH)₂D₃ suggest that the stimulation of bone resorption can be dissociated from effects on differentiation of cells of the monocyte lineage. Thus it is most likely that 1,25-(OH)₂D₃ exerts its direct effects on osteoblasts, which then activate mature osteoclasts. Rapid effects on calcium translocation have been noted. The possible role of these effects in the actions of vitamin D on bone are not yet known.