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Incidence of osteonecrosis of the jaw in Japanese osteoporosis patients taking minodronic acid

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Abstract

Osteonecrosis of the jaw (ONJ) associated with bisphosphonate therapy is a rare but severe side effect in osteoporosis patients. Recently, the number of osteoporosis patients with ONJ has dramatically increased in Japan. This has contributed to an increase in the number of patients avoiding extractions. However, there has been no prospective study providing definitive incidence data for ONJ in Japanese patients. The purpose of this study was to elucidate the true as well as suspected incidence of ONJ. A total of 3229 subjects (1612 subjects in the minodronic acid group and 1617 subjects in the raloxifene group) in the Japanese Osteoporosis Intervention Trial protocol number 4 participated in this study. ONJ was diagnosed by experienced dentists. Suspected Stage 0 and 1 (bone exposure of the jaw) ONJ was assessed by a structured questionnaire at baseline and at 6, 12, 18, and 24 months. No established ONJ cases were diagnosed during the study. The incidence of suspected Stage 0 and/or Stage 1 ONJ was 6.14 per 1000 patient-years in the minodronic acid group and 3.38 per 1000 patient-years in the raloxifene group [hazard ratio (95% confidence interval) = 1.82 (0.84–3.93), P = 0.13]. Approximately 50–60% of bone exposures that appeared during the study had disappeared at the next observation. Although the subjects in this study may have developed a greater interest in the health of the oral cavity, the incidence of ONJ after minodronic acid treatment would be lower than the expected incident rate.

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Acknowledgements

The authors express their thanks to the chairman, Dr Rikushi Morita, and the members of the ethics committee, Ms Mamiko Matsumura, Dr Tetsuro Inoue, Dr Isao Yoshimura, Dr Mitsuyoshi Nakajima, Tooru Ebihara RPh, and Mr Shinya Hattori. The authors would also like to thank those who participated as clinical investigators in JOINT-04. This JOINT study was sponsored by the Public Health Research Foundation. This study was also supported in part by funding from the Project Promoting Clinical Trials for Development of New Drugs (17lk0201061h0002) from the AMED (Japan Agency for Medical Research and Development) to ST. We thank Helen Jeays, BDSc AE, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Radiology, School of Dentistry, Matsumoto Dental University, 1780 Hirooka Gobara, Shiojiri, Nagano, 399-0781, Japan

    Akira Taguchi

  2. Biostatistics Division, Central Coordinating Unit, Clinical Research Support Center, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yukari Uemura

  3. Department of Clinical Biostatistics/Clinical Biostatistics Course, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Takumi Imai & Shiro Tanaka

  4. Clinical Medical Research Center, International University of Health and Welfare, Women’s Medical Center, Sanno Medical Center, 8-5-35 Akasaka, Minato-ku, Tokyo, 107-0052, Japan

    Hiroaki Ohta

  5. Touto Sangenjaya Rehabilitation Hospital, 1-24-3 Sangenjaya, Setagaya-ku, Tokyo, 154-0024, Japan

    Toshitaka Nakamura

  6. Japan Osteoporosis Foundation, 2-14 Odenma-cho, Nihonbashi, Kobune-cho, Chuo-ku, Tokyo, 103-0011, Japan

    Hajime Orimo

  7. Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan

    Toshitsugu Sugimoto

  8. Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan

    Satoshi Soen

  9. Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan

    Masataka Shiraki

  10. Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano, 399-0781, Japan

    Akira Taguchi

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  1. Akira Taguchi
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  2. Yukari Uemura
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  3. Takumi Imai
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Adequate Treatment of Osteoporosis (A-TOP) research group

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Correspondence to Akira Taguchi.

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Conflict of interest

AT received consultancy or lecture fees from Asahikasei Pharmaceutical Co., Teijin Pharma, Ono Pharmaceutical Co., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., and Daiichi Sankyo Co. YU received a consultancy fee from Teijin Pharma. ST has received lecture fees from Astra-Zeneca, Taiho, and Ono Pharmaceutical Co. He has received consultation fees from DeNA Life Science and CanBus. He has received outsourcing fees from Satt and Asahi Kasei Pharma. His wife has been engaged in a research project for Bayer. HO received fees from Pfizer Japan Inc. TS has received research grants from Astellas Pharma, Eisai, Daiichi Sankyo, Chugai Pharmaceutical, and Eli Lilly Japan as well as consulting and/or lecture fees from Asahi Kasei Pharma and Daiichi Sankyo. SS received lecture and consultancy fees from Asahikasei Pharmaceutical Co., Astellas Pharma, Chugai Pharmaceutical Co., Daiichi Sankyo Co., Eisai Co., Eli Lilly Japan, Ono Pharmaceutical Co., Pfizer Co., and Takeda Pharmaceutical Co. MS received lecture and consultancy fees from Asahikasei Pharma and Teijin Pharma. TI, TN, and HO declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Taguchi, A., Uemura, Y., Imai, T. et al. Incidence of osteonecrosis of the jaw in Japanese osteoporosis patients taking minodronic acid. J Bone Miner Metab 37, 886–892 (2019). https://doi.org/10.1007/s00774-019-00990-5

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