Kanatani M, Sugimoto T, Kaji H, Kano J, Chihara K. Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with calcitriol. Eur J Endocrinol 1995;133:618–25. ISSN 0804–4643
22-Oxacalcitriol (OCT), a synthetic vitamin D3 analog, can mimic the ability of calcitriol to differentiate leukemia and skin cells, to enhance the immune response and to suppress parathyroid hormone secretion, but has much less calcemic activity than that of calcitriol. The mechanism of this selective action remains not fully understood, and the actions of OCT on bone metabolism are little known. The present study was, therefore, designed to investigate the effects of OCT and calcitriol on: the proliferation and functions of osteoblastic MC3T3-E1 cells; osteoclast-like cell formation from hemopoietic blast cells in the absence of stromal cells as well as from unfractionated bone cells in the presence of stromal cells; bone resorption; and the proliferation of MC3T3-E1 cells via monocytes. 22-Oxacalcitriol and calcitriol inhibited [3H]thymidine (TdR) incorporation, alkaline phosphatase activity and collagen synthesis of MC3T3-E1 cells to a similar degree. Both OCT (10−10–10−8 mol/l) and calcitriol significantly and similarly stimulated osteoclast-like cell formation from both hemopoietic blast cells and unfractionated bone cells. 22-Oxacalcitriol (10−10 and 10−8 mol/l) significantly stimulated bone resorption, although to a slightly lesser degree than did calcitriol. Human monocyte-conditioned medium (CM) significantly stimulated TdR incorporation into MC3T3-E1 cells. On the other hand, CM obtained from monocytes treated with calcitriol (10−10–10−8 mol/l) significantly inhibited TdR incorporation in a dose-related fashion, whereas CM obtained from monocytes treated with OCT (10−10–10−8 mol/l) significantly stimulated TdR incorporation in a dose-related fashion. Thus, the actions of OCT on osteoblasts, osteoclast precursor cells and mature osteoclasts, possibly via osteoblasts, are mostly similar to those of calcitriol in vitro. The low activity of OCT in mobilizing calcium from bone in vivo, therefore, appears to be due to some other factor. OCT and calcitriol differed only in their indirect effects on the proliferation of osteoblasts via monocytes, possibly through modulating the release from monocytes of local factors that affect bone remodelling.
Toshitsugu Sugimoto, Third Division, Department of Medicine, Kobe University School of Medicine, Kobe, Japan