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Abaloparatide dose-dependently increases bone mineral density in postmenopausal women with osteoporosis: a phase 2 study

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

This study aimed to determine the efficacy of abaloparatide in increasing bone mineral density (BMD) and its safety in postmenopausal Japanese women with osteoporosis.

Materials and methods

Randomized, double-blind, placebo-controlled, dose-finding study of abaloparatide in postmenopausal Japanese women at high fracture risk. The primary endpoint was the change in lumbar spine (LS) BMD from baseline at the last visit after daily subcutaneous injections of placebo or 40 or 80 µg abaloparatide. Other endpoints included time-course changes in LS BMD at 12, 24, and 48 weeks, in total hip (TH) and femoral neck (FN) BMDs, and in bone turnover markers.

Results

Increases in LS BMD with 40 and 80 µg abaloparatide were significantly higher than that with placebo (6.6% and 11.5%, respectively), with significant between-group differences for the abaloparatide groups (4.9%). TH BMD increased by 0.4%, 1.6%, and 2.9% and FN BMD increased by 0.6%, 1.5%, and 2.4% in the placebo and 40 and 80 µg abaloparatide groups, respectively. Serum PINP rapidly increased by 67.3% and 140.7% and serum CTX slowly increased by 16.4% and 34.5% in the 40 and 80 µg abaloparatide groups, respectively. Although more adverse events were observed in the abaloparatide groups, they were mild to moderate and not dose dependent.

Conclusion

In postmenopausal Japanese women with osteoporosis at high fracture risk, abaloparatide for 48 weeks dose-dependently increased LS, TH, and FN BMDs, supporting further investigation with 80 μg abaloparatide for the treatment of osteoporosis in this population.

Trial registration number

JapicCTI-132381.

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Data availability

Restrictions apply to the availability of some or all of the data generated or analyzed during this study to preserve patient confidentiality or because they were used under license.

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Acknowledgements

The authors thank Dr. Tetsuo Nakano for his advice on radiographic assessment. Teijin Pharma Ltd., in conjunction with the Clinical Development Administration Department and outside consultants, developed the study protocol and statistical analysis plan and analyzed the data. Data were collected by the investigators at the study sites listed below. The investigators are listed below in alphabetic order: Dr. Hideki Hanashi, Medical Corp. SEIKOUKAI New Medical Research System Clinic, Tokyo, Japan; Dr. Hiroshi Nakatani, Bio-Iatoric Center, Research Center for Clinical Pharmacology, Kitasato University, Tokyo, Japan; Dr. Manabu Nakayama, Yokohama Motomachi Clinic, Kanagawa, Japan; Dr. Yasuhiro Nemoto, Nemoto Surgery and Orthopedic Surgery, Saitama, Japan; Dr. Munechika Noguchi, IHL Shinagawa East One Medical Clinic, Tokyo, Japan; Dr. Fumitoshi Omura, Koenji Orthopedic Surgery, Tokyo, Japan; Dr. Masanari Omata, Ooimachi Orthopedic and Surgical Clinic, Tokyo, Japan; Dr. Hiroshi Shimomura, Musashino Total Clinics, Tokyo, Japan; Dr. Kazuo Suzuki, Suzuki Clinic, Tokyo, Japan; Dr. Takashi Yokoyama, Daisan Kitashinagawa Hospital, Tokyo, Japan. The authors especially thank Mr. Shohei Tateishi, Teijin Pharma Ltd. and Ms. Maki Mihoya while at Teijin Pharma Ltd. for their contribution to data management and statistical analysis. The authors also thank Dr. Yoshiaki Azuma, PhD, and Mr. Hironori Arizono, MS, Teijin Pharma Ltd., for their comments during the development of the manuscript, and Dr. Bruce Mitlak, MD, Radius Health, Inc., for careful review and editing of the manuscript. Writing support for the development of the manuscript was provided by Michiko Kato and Kae Uetani of Statcom Co., Ltd. with funding from Teijin Pharma Ltd.

Funding

The study was sponsored by the Teijin Pharma Ltd., Tokyo, Japan.

Author information

Authors and Affiliations

  1. Fujii Memorial Institute of Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima, 770-8503, Japan

    Toshio Matsumoto

  2. Department of Nuclear Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan

    Teruki Sone

  3. Division of Pharmaceutical Development and Production, Teijin Pharma Limited, Tokyo, Japan

    Akiko Yamashita

  4. Aoyama General Hospital, Aichi, Japan

    Tetsuo Inoue

Authors
  1. Toshio Matsumoto
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  2. Teruki Sone
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  3. Akiko Yamashita
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  4. Tetsuo Inoue
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Contributions

The study was jointly designed by the authors and the sponsor, Teijin Pharma Ltd. All authors contributed to the study conception and design. The sponsor was responsible for quality control. TM, TS, and TI discussed the interpretation of the data and the conclusions of the manuscript with the sponsor. The sponsor was responsible for data analyses for publication. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Toshio Matsumoto.

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Conflict of interest

Toshio Matsumoto has received consulting fees from Amgen, Daiichi-Sankyo, and Teijin Pharma Ltd. Teruki Sone has received research grants from Asahi Kasei Pharma Corp. and Teijin Pharma Ltd. and consulting fees from Kissei Pharmaceutical Co. Ltd. and Shimadzu Corp. Akiko Yamashita is an employee of Teijin Pharma Ltd. Tetsuo Inoue has received consulting fees from Teijin Pharma Ltd.

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Matsumoto, T., Sone, T., Yamashita, A. et al. Abaloparatide dose-dependently increases bone mineral density in postmenopausal women with osteoporosis: a phase 2 study. J Bone Miner Metab 41, 807–816 (2023). https://doi.org/10.1007/s00774-023-01455-6

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  • DOI: https://doi.org/10.1007/s00774-023-01455-6

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