Eldecalcitol is less effective in suppressing parathyroid hormone compared to calcitriol in vivo

Abstract

Eldecalcitol is a vitamin D 3 analog under clinical development for the treatment of osteoporosis. Previous studies have shown that the binding activities of eldecalcitol to the serum vitamin D binding protein (DBP) and the vitamin D receptor (VDR) are 421.9% and 44.6% of those of calcitriol, respectively, and also, suppressed parathyroid hormone (PTH) production by only 3.5% of calcitriol in vitro using bovine parathyroid cell primary culture. Here, we compared in vivo activities of eldecalcitol on serum calcium, BMD and PTH with those of calcitriol. Six-week old male rats were given either vehicle (medium chain triglyceride; n = 6), eldecalcitol (0.025, 0.05, 0.1, 0.25, 0.5 μg/kg; n = 6) or calcitriol (0.25, 0.5, 1.0, 2.5, 5 μg/kg; n = 6) daily for 14 days by oral gavages. Eldecalcitol was approximately five-times more potent than calcitriol in increasing serum calcium. Eldecalcitol significantly increased lumbar spine BMD, however, calcitriol had no effect on BMD at any given doses. On the contrary, eldecalcitol did not affect PTH mRNA synthesis at the normocalcemic doses, despite the BMD was higher than normal. These observations indicate that, as previous in vitro study suggested, eldecalcitol is less effective in suppressing PTH compared to calcitriol.