Skip to main content
SpringerLink
Log in

Eldecalcitol

A Review of its Use in the Treatment of Osteoporosis

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

An Erratum to this article was published on 01 December 2011

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table II
Table III
Table IV
Table V
Table VI
Table VII
Fig. 2

Similar content being viewed by others

References

  1. MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008 Feb 5; 148(3): 197–213

    PubMed  Google Scholar 

  2. World Health Organization. Prevention and management of osteoporosis [online]. Available from URL: http://whqlibdoc.who.int/trs/who_trs_921.pdf [Accessed 2010 Sep 28]

  3. National Osteoporosis Guideline Group. Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK [online]. Available from URL: http://www.shef.ac.uk/NOGG/NOGG_Pocket_Guide_for_Healthcare_Professionals.pdf [Accessed 2010 Nov 19]

  4. Kanis JA, McCloskey EV, Johansson H, et al. Approaches to the targeting of treatment for osteoporosis. Nat Rev Rheumatol 2009 Aug; 5(8): 425–31

    Article  PubMed  CAS  Google Scholar 

  5. Fujiwara S. Epidemiology of osteoporosis in Japan. J Bone Mineral Metab 2005; 23 Suppl. 1: 81–3

    Article  Google Scholar 

  6. International Osteoporosis Foundation. About osteoporosis [online]. Available from URL: http://www.iofbonehealth.org/health-professionals/about-osteoporosis/epidemiology.html [Accessed 2010 Dec 13]

  7. World Health Organization. WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level: summary meeting report May 2004 [online]. Available from URL: http://who.int/chp/topics/Osteoporosis.pdf [Accessed 2010 Sep 28]

  8. Gruntmanis U. Male osteoporosis: deadly, but ignored. Am J Med Sci 2007 Feb; 333(2): 85–92

    Article  PubMed  Google Scholar 

  9. Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002 Nov 2; 359(9321): 1929–36

    Article  PubMed  Google Scholar 

  10. Orimo H, Hayashi Y, Fukunaga M, et al. Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 2001; 19(6): 331–7

    Article  PubMed  CAS  Google Scholar 

  11. Bikle DD. What is new in vitamin D: 2006–2007. Curr Opin Rheumatol 2007 Jul; 19(4): 383–8

    Article  PubMed  CAS  Google Scholar 

  12. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006 Mar; 81(3): 353–73

    Article  PubMed  CAS  Google Scholar 

  13. Office of Dietary Supplements NIH. Dietary supplement fact sheet: vitamin D [online]. Available from URL: http://ods.od.nih.gov/factsheets/vitamind/ [Accessed 2010 Nov 6]

  14. Saag KG, Geusens P. Progress in osteoporosis and fracture prevention: focus on postmenopausal women. Arthritis Res Ther 2009; 11(5): E251

    Article  Google Scholar 

  15. Nishii Y. Rationale for active vitamin D and analogs in the treatment of osteoporosis. J Cell Biochem 2003 Feb 1; 88(2): 381–6

    Article  PubMed  CAS  Google Scholar 

  16. Jones G. Vitamin D analogs. Endocrinol Metab Clin North Am 2010; 39(2): 447–72

    Article  PubMed  CAS  Google Scholar 

  17. Edirol® (eldecalcitol tablets): Japanese prescribing information. Tokyo: Chugai, 2011

  18. Kubodera N, Tsuji N, Uchiyama Y, et al. A new active vitamin D analog, ED-71, causes increase in bone mass with preferential effects on bone in osteoporotic patients. J Cell Biochem 2003 Feb 1; 88(2): 286–9

    Article  PubMed  CAS  Google Scholar 

  19. Matsumoto T, Takano T, Yamakido S, et al. Comparison of the effects of eldecalcitol and alfacalcidol on bone and calcium metabolism. J Steroid Biochem Mol Biol 2010 Jul; 121(1–2): 261–4

    Article  PubMed  CAS  Google Scholar 

  20. Hatakeyama S, Nagashima S, Imai N, et al. Synthesis and biological evaluation of a 3-positon epimer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71). J Steroid Biochem Mol Biol 2007 Mar; 103(3–5): 222–6

    Article  PubMed  CAS  Google Scholar 

  21. Uchiyama Y, Higuchi Y, Takeda S, et al. ED-71, a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis. Bone 2002 Apr; 30(4): 582–8

    Article  PubMed  CAS  Google Scholar 

  22. Matsumoto T, Miki T, Hagino H, et al. A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 2005 Sep; 90(9): 5031–6

    Article  PubMed  CAS  Google Scholar 

  23. 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. Epub 2011 Jul 19

  24. Ito M, Nakamura T, Fukunaga M, et al. Effect of eldecalcitol, an active vitamin D analog, on hip structure and biomechanical properties: 3D assessment by clinical CT. Bone 2011 Sep; 49(3): 328–34

    Article  PubMed  CAS  Google Scholar 

  25. Abe M, Tsuji N, Takahashi F, et al. Overview of the clinical pharmacokinetics of eldecalcitol, a new active vitamin D3 derivative. Jpn Pharmacol Ther 2011; 39(3): 261–74

    CAS  Google Scholar 

  26. Miyata K, Abe M, Terao K, et al. Pharmacokinetics of eldecalcitol in primary osteoporosis patients: randomized, double-blind, multicentre, long-term phase III clinical study. Jpn Pharmacol Ther 2011; 39(3): 299–307

    CAS  Google Scholar 

  27. Miyata K, Ohba Y, Abe M, et al. Effects of eldecalcitol on the pharmacokinetics of the CYP3A4 substrate, simvastatin: double blind, randomized, placebo-controlled, parallel group comparative study in healthy male volunteers. Jpn Pharmacol Ther 2011; 39(3): 275–85

    CAS  Google Scholar 

  28. Ikeda Y, Kumagai Y, Arinaga T, et al. Open-label, multicentre, single dose study of eldecalcitol pharmacokinetics in patients with impaired liver function. Jpn Pharmacol Ther 2011; 39(3): 287–97

    CAS  Google Scholar 

  29. Matsumoto T, Kubodera N. ED-71, a new active vitamin D3, increases bone mineral density regardless of serum 25(OH)D levels in osteoporotic subjects. J Steroid Biochem Mol Biol 2007 Mar; 103(3–5): 584–6

    Article  PubMed  CAS  Google Scholar 

  30. Cheung AM, Detsky AS. Osteoporosis and fractures: missing the bridge? JAMA 2008 Mar 26; 299(12): 1468–70

    Article  PubMed  CAS  Google Scholar 

  31. Qaseem A, Snow V, Shekelle P. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2008 Sep 16; 149(6): 404–15

    PubMed  Google Scholar 

  32. Committee of Japanese Guidelines for the Prevention and Treatment of Osteoporosis. The Japanese guidelines for the prevention and treatment of osteoporosis (2006) edition-abridged). Osteoporosis Japan 2007; 15(2): 221–5

    Google Scholar 

  33. Papadimitropoulos E, Wells G, Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VIII: meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Endocrine Rev 2002 Aug; 23(4): 560–9

    CAS  Google Scholar 

  34. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005 May 11; 293(18): 2257–64

    Article  PubMed  CAS  Google Scholar 

  35. Richy F, Schacht E, Bruyere O, et al. Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int 2005; 76(3): 176–86

    Article  PubMed  CAS  Google Scholar 

  36. Avenell A, Gillespie WJ, Gillespie LD, et al. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009; (2): CD000227

  37. Ringe JD. Absolute risk reduction in osteoporosis: assessing treatment efficacy by number needed to treat. Rheumatol Int 2010 May; 30(7): 863–9

    Article  PubMed  CAS  Google Scholar 

  38. Sellmeyer DE. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA 2010 Oct 6; 304(13): 1480–4

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, Auckland, 0754, New Zealand

    Mark Sanford & Paul L. McCormack

Authors
  1. Mark Sanford
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul L. McCormack
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Sanford.

Additional information

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.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanford, M., McCormack, P.L. Eldecalcitol. Drugs 71, 1755–1770 (2011). https://doi.org/10.2165/11206790-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11206790-000000000-00000

Keywords

Search

Navigation