[Biological activity of calcitriol and its new analogues -- potential therapeutic applications]

Abstract

Calcitriol is effective not only in the regulation of calcium-phosphate homeostasis, but also in promoting the differentiation and inhibition of proliferation of various cells. Calcitriol seems to be a potent drug with various therapeutic applications, such as regulation of calcium-phosphate homeostasis and treatment of psoriasis, autoimmune diseases, and cancer. Since clinical use of calcitriol is largely limited, due to its undesirable side effect of hypercalcemia, numerous calcitriol analogues have been synthesized to obtain compounds with better therapeutic profiles. This paper summarizes the current state of knowledge concerning the cellular mechanisms of calcitriol's biological activity and their clinical implications. Such medical application includes treatment (as a single-drug or in combination) of osteoporosis, renal osteodystrophy, psoriasis (calcipotriol or tacalcitol ointment), autoimmunological diseases (including multiple sclerosis), and some cancers. The efforts to obtain new vitamin D3 analogues are also briefly reviewed. The structures and roles of vitamin D receptors in the biological effects of calcitriol and its analogues are discussed.