Regulation of bone cells by 1,25(OH)2D3

tion; formation Bone is a remarkable organ in that it is always new, due to the process called remodelling where, even in the elderly individual, old bone is regularly replaced by new bone. Osteoclasts resorb bone, osteoblasts form a matrix and the matrix is subsequently mineralized to form new bone in approximately 200 days [1]. In this review we discuss the direct effects of vitamin D on osteoclasts and bone resorption, and on osteoblasts and bone formation, and discuss the possibility of using new vitamin D analogues with selective effects on bone cells. Finally we address the question of whether vitamin D could be used as a treatment for osteoporosis. The osteoclast is a cell which develops in the bone marrow from progenitor cells related to the monocytic lineage [2]. In bone marrow cultures, it is possible to stimulate the progenitor cells to form preosteoclasts, which subsequently mature into osteoclasts. This constitutes one mechanism whereby vitamin D can influence the osteoclasts and bone resorption [2]. Vitamin D3 also stimulates the activity of existing osteoclasts. Raisz et al. showed in 1972, by using a model of foetal rat long bones, that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol] stimulates bone resorption [3]. They treated the bones with either 1,25(OH)2D3 or calcidiol and found that there was a dose-dependent stimulation of bone resorp-tion with both agents, and that calcitriol was about 100 times more potent than calcidiol. This resorptive effect was significant within hours, demonstrating that it could not be due to formation of new osteoclasts [3]. Since then we have learned that the stimulation, i.e. the capacity to stimulate osteoclasts to resorb bone, actually resides within the osteoblasts [4]. This means that when osteoblasts are challenged with agents that enhance bone resorption, they stimulate the latent osteoclasts to start resorbing bone, and they probably also stimulate the formation of osteoclasts. In th