Eldecalcitol for the treatment of osteoporosis

Abstract

Eldecalcitol (1α, 25-dihydroxy-2β-[3-hydroxypropyloxy] vitamin D3; ED-71) is a new analog of the active form of vitamin D. Eldecalcitol has recently been approved for the treatment of osteoporosis in Japan. In addition to regulation of calcium metabolism carried out by conventional vitamin D analogs, eldecalcitol possesses a strong inhibitory effect on bone resorption and causes a significant increase in bone mineral density. A Phase III clinical trial on osteoporosis showed that eldecalcitol reduced the incidence of new vertebral fractures over 3 years by 26% compared with alfacalcidol. Although the overall risk of nonvertebral fractures was not reduced by eldecalcitol, the risk of wrist fracture was decreased significantly in the eldecalcitol group (71%) compared with the alfacalcidol group. The serum level of 25-hydroxyvitamin D (25[OH]D) was normalized by supplementation of native vitamin D in this trial, so the desirable effects on bone by eldecalcitol were considered to be derived from its distinctive pharmacological action. Increased blood calcium was observed in 21% of patients treated with eldecalcitol, and hypercalcemia (>11.5 mg/dL) occurred in 0.4% of eldecalcitol recipients, so serum calcium concentration should be monitored after starting eldecalcitol treatment. Eldecalcitol has dual effects on the metabolism of bone and calcium and is useful for the treatment of osteoporosis, especially for elderly patients (who frequently suffer from vitamin D deficiency). This article reviews the clinical efficacy and safety of eldecalcitol in the treatment of osteoporosis.

Keywords: bone mineral density; nonvertebral fracture; osteoporosis; vitamin D.

Figure 1

Chemical structures of native vitamin D₃ and active vitamin D₃ analogs.

Figure 2

Incidence of new vertebral fractures in the alfacalcidol (1.0 μg/day) group and the eldecalcitol (0.75 μg/day) group during the 3-year study period. Kaplan–Meier estimates of the incidence of new vertebral fractures. Adapted from Matsumoto T, Ito M, Hayashi Y, et al. A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures – a randomized, active comparator, double-blind study. Bone. 2011;49(4):605–612, with permission from Elsevier. Abbreviation: CI, confidence interval.

Figure 3

Incidence of all nonvertebral fractures, nonvertebral fractures at three major sites (humerus, wrist, hip), and wrist fracture in the alfacalcidol (1.0 μg/day) group and the eldecalcitol (0.75 μg/day) group during the 3-year study period. Notes: *P = 0.009. Data from. Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 4

Effects of eldecalcitol and alfacalcidol on BMD (A and B) and bone turnover markers (C and D) during the 3-year study period. Notes: Mean percent change from baseline in lumbar spine (A) and total hip (B) BMD in the eldecalcitol group (closed circle) and the alfacalcidol group (open circle) during the study period. Median percent change from baseline in bone turnover markers including serum BSAP (C) and urinary NTX (D) in the eldecalcitol group (closed circle) and the alfacalcidol group (open circle) during the study period are shown. Data are means ± SE for lumbar spine and total hip BMD, and medians for bone turnover markers. *P < 0.001 in comparison with alfacalcidol. Adapted from Matsumoto T, Ito M, Hayashi Y, et al. A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures – a randomized, active comparator, double-blind study. Bone. 2011;49(4):605–612, with permission from the Elsevier. Abbreviations: BMD, bone mineral density; BSAP, bone-specific alkaline phosphatase; NTX, urinary N-terminal propeptide of type I collagen; SE, standard error.