Skip to main content

Advertisement

SpringerLink
Log in

The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese male patients with osteoporosis

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

We conducted a post-marketing observational study to investigate the safety and effectiveness of eldecalcitol for the treatment of osteoporosis in a Japanese clinical setting. The observation period was 12 months for women and 36 months for men. The final results for the female patients have already been published. In this article, the final results for the male patients are reported. A total of 470 male osteoporosis patients were enrolled. The safety analysis set included 431 patients (mean age, 76.8 years; mean ± SD follow-up period, 631.0 ± 450.3 days), and 175 patients continued treatment throughout the 3-year observational period. Adverse drug reactions (ADRs) were reported in 28 patients (6.49%); the most common ADRs were hypercalcemia (1.16%) and renal impairment (1.16%). Serious ADRs were reported in 5 patients (1.16%). Mean serum calcium was within the normal range throughout the observation period. The cumulative incidence of new vertebral and nonvertebral fractures at 36 months, estimated by Kaplan–Meier analysis, was 10.23 and 4.06%, respectively. At the last observation, mean lumbar spine bone mineral density was 3.49% higher (P < 0.0001) than at baseline, and levels of the bone turnover markers BAP and TRACP-5b were reduced (–14.64%; P = 0.0009, and − 29.51%; P < 0.0001, respectively). In conclusion, the safety and effectiveness of eldecalcitol for the treatment of Japanese male osteoporosis patients was confirmed in clinical practice. Careful monitoring of serum calcium and estimated glomerular filtration rate, both before and during treatment, is necessary to minimize the risk of hypercalcemia and renal impairment while maximizing the effectiveness of eldecalcitol.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gullberg B, Johnell O, Kanis JA (1997) World-wide projections for hip fracture. Osteoporos Int 7:407–413

    Article  CAS  PubMed  Google Scholar 

  2. Editorial Committee on Guidelines for Prevention and Treatment of Osteoporosis (2015) Guidelines for prevention and treatment of osteoporosis. Japan Osteoporosis Society, Tokyo, Japan (in Japanese)

  3. Orimo H, Yaegashi Y, Hosoi T, Fukushima Y, Onoda T, Hashimoto T, Sakata K (2016) Hip fracture incidence in Japan: estimates of new patients in 2012 and 25-year trends. Osteoporos Int 27:1777–1784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Xu Z, Fan C, Zhao X, Tao H (2016) Treatment of osteoporosis with eldecalcitol, a new vitamin D analog: a comprehensive review and meta-analysis of randomized clinical trials. Drug Des Devel Ther 10:509–517

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Matsumoto T, Miki T, Hagino H, Sugimoto T, Okamoto S, Hirota T, Tanigawara Y, Hayashi Y, Fukunaga M, Shiraki M, Nakamura T (2005) 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 90:5031–5036

    Article  CAS  PubMed  Google Scholar 

  6. Matsumoto T, Ito M, Hayashi Y, Hirota T, Tanigawara Y, Sone T, Fukunaga M, Shiraki M, Nakamura T (2011) A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures—a randomized, active comparator, double-blind study. Bone 49:605–612

    Article  CAS  PubMed  Google Scholar 

  7. Sakai A, Ito M, Tomomitsu T, Tsurukami H, Ikeda S, Fukuda F, Mizunuma H, Inoue T, Saito H, Nakamura T, e-ADVANCED Study Group (2015) Efficacy of combined treatment with alendronate (ALN) and eldecalcitol, a new active vitamin D analog, compared to that of concomitant ALN, vitamin D plus calcium treatment in Japanese patients with primary osteoporosis. Osteoporos Int 26:1193–1202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Saito H, Kakihata H, Nishida Y, Yatomi S, Nihojima S, Kobayashi Y, Tabata H, Nomura M (2017) The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese patients with osteoporosis: interim report. J Bone Miner Metab 35:456–463

    Article  CAS  PubMed  Google Scholar 

  9. Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H, Osteoporosis Diagnostic Criteria Review Committee: Japanese Society for Bone and Mineral Research (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337

    Article  CAS  PubMed  Google Scholar 

  10. Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A (2000) Alendronate for the treatment of osteoporosis in men. N Engl J Med 343:604–610

    Article  CAS  PubMed  Google Scholar 

  11. Ringe JD, Dorst A, Faber H, Ibach K (2004) Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study. Rheumatol Int 24:110–113

    Article  CAS  PubMed  Google Scholar 

  12. Ringe JD, Farahmand P, Faber H, Dorst A (2009) Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study. Rheumatol Int 29:311–315

    Article  CAS  PubMed  Google Scholar 

  13. Boonen S, Orwoll ES, Wenderoth D, Stoner KJ, Eusebio R, Delmas PD (2009) Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study. J Bone Miner Res 24:719–725

    Article  CAS  PubMed  Google Scholar 

  14. Orwoll ES, Binkley NC, Lewiecki EM, Gruntmanis U, Fries MA, Dasic G (2010) Efficacy and safety of monthly ibandronate in men with low bone density. Bone 46:970–976

    Article  CAS  PubMed  Google Scholar 

  15. Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S, HORIZON Recurrent Fracture Trial (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809

    Article  CAS  PubMed  Google Scholar 

  16. Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J et al (2012) Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med 367:1714–1723

    Article  CAS  PubMed  Google Scholar 

  17. Orwoll ES, Miller PD, Adachi JD, Brown J, Adler RA, Kendler D, Bucci-Rechtweg C, Readie A, Mesenbrink P, Weinstein RS (2010) Efficacy and safety of a once-yearly i.v. infusion of zoledronic acid 5 mg versus a once-weekly 70-mg oral alendronate in the treatment of male osteoporosis: a randomized, multicenter, double-blind, active-controlled study. J Bone Miner Res 25:2239–2350

    Article  CAS  PubMed  Google Scholar 

  18. Orwoll E, Teglbjærg CS, Langdahl BL, Chapurlat R, Czerwinski E et al (2012) A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab 97:3161–3169

    Article  CAS  PubMed  Google Scholar 

  19. Langdahl BL, Teglbjærg CS, Ho PR, Chapurlat R, Czerwinski E et al (2015) A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab 100:1335–1342

    Article  CAS  PubMed  Google Scholar 

  20. Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, Kaufman JM, Clancy AD, Gaich GA (2003) The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18:9–17

    Article  CAS  PubMed  Google Scholar 

  21. Kaufman JM, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, Lindsay R, Mitlak BH (2005) Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 16:510–516

    Article  CAS  PubMed  Google Scholar 

  22. Kondo S, Takano T, Ono Y, Saito H, Matsumoto T (2015) Eldecalcitol reduces osteoporotic fractures by unique mechanisms. J Steroid Biochem Mol Biol 148:232–238

    Article  CAS  PubMed  Google Scholar 

  23. Japanese package insert for Edirol® Capsule. 2016. Online. Available: https://chugai-pharm.jp/hc/ss/pr/drug/edr_cap0075/pi/PDF/edr_pi.pdf. Accessed May, 2017 (in Japanese)

  24. Tomková S, Telepková D, Vanuga P, Killinger Z, Sulková I, Celec P, Payer J (2014) Therapeutic adherence to osteoporosis treatment. Int J Clin Pharmacol Ther 52:663–668

    Article  PubMed  Google Scholar 

  25. Weycker D, Macarios D, Edelsberg J, Oster G (2006) Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int 17:1645–1652

    Article  CAS  Google Scholar 

  26. Kim SY, Schneeweiss S, Liu J, Daniel GW, Chang CL, Garneau K, Solomon DH (2010) Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Res Ther 12:R154

    Article  PubMed  PubMed Central  Google Scholar 

  27. Weiss RJ, Wick MC, Ackermann PW, Montgomery SM (2010) Increased fracture risk in patients with rheumatic disorders and other inflammatory diseases: a case-control study with 53,108 patients with fracture. J Rheumatol 37:2247–2250

    Article  PubMed  Google Scholar 

  28. Fan Y, Wei F, Lang Y, Liu Y (2016) Diabetes mellitus and risk of hip fractures: a meta-analysis. Osteoporos Int 27:219–228

    Article  CAS  PubMed  Google Scholar 

  29. Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505

    Article  PubMed  Google Scholar 

  30. Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a metaanalysis. Osteoporos Int 18:427–444

    Article  CAS  PubMed  Google Scholar 

  31. Gregson CL, Dennison EM, Compston JE, Adami S, Adachi JD et al (2014) Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study. Osteoporos Int 25:85–95

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the efforts of the physicians and patients who participated in the study. This study was sponsored by Chugai Pharmaceutical Co., Ltd, with considerable support from Taisho Toyama Pharmaceutical Co., Ltd. The authors would like to thank Kokoro Hayashi, PhD, and Rie Ishibashi of inScience Communications, Springer Healthcare (Tokyo, Japan) for providing editorial support, which was funded by Chugai Pharmaceutical Co., Ltd (Tokyo, Japan).

Author information

Authors and Affiliations

  1. Medical Science Department, Medical Affairs Division, Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi, 2-Chome, Chuo-ku, Tokyo, 103-8324, Japan

    Satoshi Kondo

  2. Pharmacovigilance Department, Administration Division, Taisho Toyama Pharmaceutical Co., Ltd, 3-25-1 Takada, Toshima-ku, Tokyo, 170-8635, Japan

    Yumiko Kobayashi

  3. Real World Data Science Department, Drug Safety Division, Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi, 2-Chome, Chuo-ku, Tokyo, 103-8324, Japan

    Hiroyuki Kakihata & Yosuke Nishida

  4. PV & Safety Science Department, Drug Safety Division, Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi, 2-Chome, Chuo-ku, Tokyo, 103-8324, Japan

    Yuko Furuno

  5. Risk Communication Department, Drug Safety Division, Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi, 2-Chome, Chuo-ku, Tokyo, 103-8324, Japan

    Hidehiro Tabata & Makoto Nomura

Authors
  1. Satoshi Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroyuki Kakihata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yosuke Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuko Furuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yumiko Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hidehiro Tabata
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Makoto Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoshi Kondo.

Ethics declarations

Conflict of interest

All authors except YK are employees of Chugai Pharmaceutical Co., Ltd. YK is an employee of Taisho Toyama Pharmaceutical Co., Ltd.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kondo, S., Kakihata, H., Nishida, Y. et al. The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese male patients with osteoporosis. J Bone Miner Metab 37, 292–300 (2019). https://doi.org/10.1007/s00774-018-0915-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-018-0915-2

Keywords

Search

Navigation