Abstract

Eldecalcitol (1α,25[OH](2)-2β-(3-hydroxypropyloxy)vitamin D(3); ED-71; Edirol®) is an orally administered analogue of active vitamin D (calcitriol) that is available in Japan for the treatment of osteoporosis at a dosage of 0.75 μg/day. In a randomized, double-blind, placebo-controlled, dose-ranging trial, eldecalcitol reduced markers of bone turnover significantly more than placebo. Similarly, in a randomized, double-blind comparison with the calcitriol prodrug, alfacalcidol 1.0 μg/day, eldecalcitol 0.75 μg/day produced significantly greater reductions in markers of bone turnover and had a positive effect on femoral biomechanical properties. In both trials, eldecalcitol treatment was associated with an increase in bone mineral density (BMD), whereas patients who received the comparators generally had a reduction in BMD. In the comparison with alfacalcidol, eldecalcitol significantly reduced the 3-year incidence of vertebral fractures (primary endpoint), with an absolute risk reduction of 4.1% over this period, representing a relative risk reduction of 26%. There was no significant difference in the rate of non-vertebral fractures. In both trials, increases in blood calcium (to >2.6 mmol/L) and urinary calcium (to >0.1 mmol/L glomerular filtrate) were the most clinically important treatment-emergent adverse events. In the comparison with alfacalcidol over 36 months of treatment, 21.0% and 13.5% of eldecalcitol 0.75 μg/day and alfacalcidol 1.0 μg/day recipients had increased blood calcium, whereas hypercalcaemia (defined as a serum calcium >2.9 mmol/L) occurred in 0.4% and urolithiasis in 1.3% of eldecalcitol recipients. Eldecalcitol is an efficacious treatment for patients with osteoporosis that should be further investigated in head-to-head trials with other recommended first-line pharmacological treatments.