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Eldecalcitol (1α,25[OH]2-2β-(3-hydroxypropyloxy)vitamin D3; ED-71; Edirol®) is an orally administered analogue of active vitamin D (calcitriol) that is available in Japan for the treatment of osteoporosis. Two randomized, double-blind, multicentre trials were conducted in patients with osteoporosis.
In a placebo-controlled, dose-ranging trial, eldecalcitol significantly reduced serum bone-specific alkaline phosphatase (BALP) and serum osteocalcin, markers of bone formation, more than placebo. Eldecalcitol at a 1.0 µg/day dosage, but not at lower dosages, also significantly reduced urinary type I collagen N-telopeptide (NTX), a marker of bone resorption, more than placebo. In a comparison with alfacalcidol (a prodrug of calcitriol), eldecalcitol produced significantly greater reductions in serum BALP and urinary NTX, and had a positive effect on CT markers of femoral biomechanical properties.
In the comparison with alfacalcidol, eldecalcitol 0.75µg/day significantly reduced the 3-year incidence of vertebral fractures, 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, eldecalcitol treatment was also associated with an increase in bone mineral density, whereas patients who received the comparators generally had a reduction in bone mineral density.
Increases in blood calcium (to >2.6mmol/L) and urinary calcium (to >0.1 mmol/L glomerular filtrate) were the most clinically important treatment-emergent adverse events. In the placebo-controlled, dose-ranging trial, 23% and 25% of patients in the eldecalcitol 1 mg/day group had increased blood and urinary calcium compared with 7% and 7%, 6% and 9%, and 0% and 1.9% in the eldecalcitol 0.5 and 0.75 µg/day, and placebo groups, respectively. In the comparison with alfacalcidol, 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 >2.9mmol/L) occurred in 0.4% and urolithiasis in 1.3% of eldecalcitol recipients over 36 months of treatment.
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.
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