Journal of Bone and Mineral Metabolism

, Volume 24, Issue 1, pp 11–15

Randomized trial comparing low-dose hormone replacement therapy and HRT plus 1α-OH-vitamin D3 (alfacalcidol) for treatment of postmenopausal bone loss


    • Department of Obstetrics and GynecologyHirosaki University School of Medicine
  • Masataka Shiraki
    • Research Institute and Practice for Involutional Diseases
  • Masafumi Shintani
    • Department of Obstetrics and GynecologyNarakenritsu Mimuro Hospital
  • Itsuo Gorai
    • Department of Obstetrics and Gynecology, International University of Health and WelfareAtami Hospital
  • Kazuya Makita
    • Department of Obstetrics and Gynecology, School of MedicineKeio University
  • Shunichi Itoga
    • Department of Obstetrics and GynecologyTone Central Hospital
  • Yoshiko Mochizuki
    • Department of Obstetrics and GynecologyDokkyo University School of Medicine
  • Hiromichi Mogi
    • Department of Obstetrics and GynecologyMaebashi Kyouritu Hospital
  • Yasuhisa Iwaoki
    • Department of Obstetrics and GynecologyKouseiren Yoshida General Hospital
  • Shouichirou Kosha
    • Department of Obstetrics and GynecologyKagoshima University School of Medicine
  • Toshiyuki Yasui
    • Department of Obstetrics and GynecologyTokushima University School of Medicine
  • Osamu Ishihara
    • Department of Obstetrics and GynecologySaitama Medical School
  • Takumi Kurabayashi
    • Department of Obstetrics and GynecologyNiigata University School of Medicine
  • Yoshio Kasuga
    • Department of Obstetrics and GynecologyAshikaga Red Cross Hospital
  • Kunihiko Hayashi
    • Department of Basic Allied Medicine, School of Health Sciences, Faculty of MedicineGunma University

DOI: 10.1007/s00774-005-0639-y

Cite this article as:
Mizunuma, H., Shiraki, M., Shintani, M. et al. J Bone Miner Metab (2006) 24: 11. doi:10.1007/s00774-005-0639-y


We conducted a prospective, randomized, multicenter, open-label 2-year trial with 76 postmenopausal women aged ≥60 years with low (T-score less than −1) lumbar bone mineral density (BMD). The hormone replacement therapy (HRT) group received a low dose of conjugated estrogen (CEE) at a dose of 0.31 mg/day ± medroxyprogesterone acetate (MPA) 2.5 mg/day. Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 µg/day. Changes in lumbar BMD measured by dual energy X-ray absorptiometry (DXA) were followed every 6 months for 2 years. The lumbar BMD of group HRT increased 3.37% [95% confidence interval (CI) 1.6%–5.2%], 4.00% (95%CI 1.6%–6.4%), and 2.32% (95%CI −0.7% to 5.3%) at 12, 18, and 24 months, respectively, when the baseline value was taken as 0%. Lumbar BMD of group HRT/D showed a significant increase beyond 6 months. The percent increases for this group at 6, 12, 18, and 24 months were 6.18 (95%CI 1.3%–6.6%), 6.18% (95%CI 3.9%–8.5%), 7.17% (95%CI 4.3%–10.0%), and 8.75% (95%CI 6.0%–11.5%), respectively. In addition, there was a significant difference in the changes of the lumbar BMD between the two groups at 24 months, suggesting that the combination of HRT and alfacalcidol is more effective than HRT alone in terms of the BMD effect. This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause.

Key words

bone losslow-dose HRTosteoporosis1α-OH-vitamin D3
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© Springer-Verlag Tokyo 2006