D-hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis management

Alfacalcidol (1-alpha-hydroxyvitamin D3) is a non-endogenous analog of vitamin D which can bypass the renal and intestinal regulatory mechanisms that control the production of calcitriol (1,25-hydroxyvitamin D3, the active form of vitamin D, D-Hormone). Alfacalcidol may be metabolized into calcitriol with a limited risk of hypercalcemia. Alfacalcidol and calcitriol have been evaluated in animal and human studies assessing their effects on bone mineral density and fracture rates. More recently, they have been shown to produce beneficial effects in muscle, immune system, and autoimmune diseases, including rheumatoid arthritis. This paper discusses the therapeutic efficacy of alfacalcidol in reports in which it has been proposed as an interesting alternative to vitamin D or calcitriol. Some recent findings about general metabolism and regulation of vitamin D and its analogs are discussed. The biological and clinical effects of alfacalcidol in post-menopausal osteoporosis are reviewed, followed by critical appraisal of its efficacy in preventing bone loss and falls in the elderly. The last two sections discuss the role of D analogs in regulating the immune system, with particular regard to rheumatoid arthritis. The main results of this review show that alfacalcidol may have a wider range of therapeutic applicability, beyond simply restricting it to patients in hemodialysis or peritoneal dialysis with high serum levels of intact PTH.