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Effect of raloxifene on bone mineral density and biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis: results from a randomized placebo-controlled trial

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Abstract

The safety and efficacy of raloxifene, a selective estrogen receptor modulator (SERM), has been studied extensively in large, global clinical trials. However, the effect of raloxifene on bone mineral density (BMD) and on biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis has not been rigorously evaluated. This study was designed to assess the safety and efficacy of raloxifene in Japanese postmenopausal women with osteoporosis following 1 year of therapy. Participants in this multicenter trial were randomly assigned to receive placebo, raloxifene 60 mg/day (RLX60), or raloxifene 120 mg/day (RLX120). Lumbar spine BMD was measured at baseline, 24, 40, and 52 weeks, and biochemical markers of bone turnover were assessed at baseline, 12, 24, and 52 weeks. Serum lipids were assessed at baseline, 12, 24, 40, and 52 weeks, and breast examinations and transvaginal ultrasound of the endometrium were performed at enrollment and 52 weeks. Compared with baseline, women taking RLX60 had significant increases in lumbar spine (L2-L4) BMD at 24 weeks (+3.3%, p<0.001) through 52 weeks (+3.5%, p<0.001) of therapy, and similar results were observed in the RLX120 group. Markers of bone turnover and total cholesterol and LDL-C were significantly reduced, and no significant treatment-group difference was observed for patients reporting at least one adverse event following randomization. In addition, there were no reported venous thromboembolic events (VTE) in any treatment group. The results of this study demonstrate that raloxifene is associated with early increases in lumbar spine BMD, has favorable effects on biochemical markers of bone turnover and lipid profile, and is well tolerated in postmenopausal Japanese women.

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Acknowledgements

This study was conducted with the support of Eli Lilly Japan KK and Chugai Pharmaceuticals. The authors would like to acknowledge the contributions of Akio Tanaka, Clinical Team Leader for Chugai Pharmaceuticals; Akio Uemura (Eli Lilly Japan KK) and Chuck Rivera (Lilly Research Laboratories) for clinical study design and coordination; Steven Watts (Lilly Research Laboratories) for statistical data analysis; and Timothy Mason and Karen Pinette (Lilly Research Laboratories) for manuscript preparation. The authors would also like to acknowledge the efforts of the the Chief Investigators of the Japan clinical trial: S. Fujimoto, Hokkaido University School of Medicine; F. Komatsuzaki, Sapporo Shirakabadai Hospital; N. Inaba, Dokkyo Medical College; H. Mizunuma, Gunma University School of Medicine; T. Sato, Onarimon Clinic; T. Nitta, Takekawa Hospital; K. Fukuda, Shiratori Clinic; K. Kinoshita, Seijokinoshita Hospital; S. Yamazaki, Sengoku Clinic; A. Itabashi, NS Clinic; K. Nakajima, Ebisu Clinic; K. Suzuki, Suzuki Clinic; S. Yagi, Kamimeguro Internal Medicine Clinic; F. Hirahara, Yokohama City University School of Medicine ; K. Tanaka, Niigata University School of Medicine; K. Inoue, Fujimikogen Hospital; K. Kaneko, Juntendo University Izunagaoka Hospital; N. Hamada, Sumire Hospital; Y. Ohtsuki, Osaka Police Hospital; Y. Kuroki, Kanebo Memorial Hospital; H. Shimada, Kobe City General Hospital; K. Katayama, West Kobe Medical Center; T. Matsuda, Kagoshima Red Cross Hospital; T. Sugimoto, Kobe University School of Medicine; S. Okamoto, Okamoto Internal Medicine Clinic. In addition, recognition is given to the Japan Raloxifene Clinical Team: K. Sato, T. Tominaga, Y. Ishikura, and H. Uchida, Chugai Pharmaceuticals; E. Hamaya, Y. Yoshimoto, J. Nagisa, Y. Hata, T. Yamamoto, and J. Yano, Eli Lilly Japan KK.

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Authors and Affiliations

  1. Osaka City University, Osaka, Japan

    H. Morii

  2. Biostatistics, School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan

    Y. Ohashi

  3. Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan

    Y. Taketani

  4. Department of Nuclear Medicine, Kawasaki Medical School, Okayama, Japan

    M. Fukunaga

  5. Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan

    T. Nakamura

  6. Department of Clinical Laboratory, Saitama Medical School, Saitama, Japan

    A. Itabashi

  7. Lilly Research Laboratories, Eli Lilly, Indianapolis, Indiana, USA

    S. Sarkar & K. Harper

  8. 2–11–25 Mukoyama, 665–0005, Takarazuka-City, Hyogo, Japan

    H. Morii

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  1. H. Morii
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  2. Y. Ohashi
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  3. Y. Taketani
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  4. M. Fukunaga
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  5. T. Nakamura
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  7. S. Sarkar
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  8. K. Harper
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The named authors wrote this article on behalf of the Japan Clinical Trial Research Group.

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Morii, H., Ohashi, Y., Taketani, Y. et al. Effect of raloxifene on bone mineral density and biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis: results from a randomized placebo-controlled trial. Osteoporos Int 14, 793–800 (2003). https://doi.org/10.1007/s00198-003-1424-1

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  • DOI: https://doi.org/10.1007/s00198-003-1424-1

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