, Volume 71, Issue 13, pp 1755-1770
Date: 24 Sep 2012

Eldecalcitol

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Abstract

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.

Various sections of the manuscript reviewed by: B. Cortet, Department of Rheumatology, University Hospital of Lille, Lille, France; E. Franek, Department of Internal Medicine, Endocrinology and Diabetology, Central Clinical Hospital, Ministry of Internal Affairs and Administration, Warsaw, Poland; J. Iwamoto, Institute for Integrated Sports Medicine, Keio University School of Medicine, Keio University, Tokyo, Japan; M. Kleerekoper, Department of Internal Medicine, St Joseph Mercy Hospital, Ann Arbor, MI, USA.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘eldecalcitol’ was identified by searching databases since 1980 (including MEDLINE, EMBASE and in-house AdisBase), bibliographies from published literature, clinical trial registries/databases and websites, including those of regional regulatory agencies and the manufacturer. Additional information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘eldecalcitol’ and ‘osteoporosis’. Searches were last updated 19 August 2011.
Selection: Studies in patients with osteoporosis who received eldecalcitol. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data were also included.
Index terms: Eldecalcitol, ED-71, vitamin D analogues, osteoporosis, osteoporotic fractures, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.
An erratum to this article is available at http://dx.doi.org/10.2165/11585710-000000000-00000.