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Efficacy of non-steroidal anti-inflammatory drugs on zoledronic acid-induced acute-phase reactions: randomized, open-label, Japanese OZ study

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Abstract

Introduction

Zoledronic acid infusion is used to treat osteoporosis but patients, especially Japanese patients, often experience acute-phase reactions (APRs). In this multicenter, randomized, open-label, parallel-group study, we examined the efficacy of the most commonly used non-steroidal anti-inflammatory drug loxoprofen in Japan in reducing the incidence rate of zoledronic acid-induced APRs and body temperature, and investigated risk/protective factors for APRs in this population.

Materials and methods

Patients aged ≥ 60 years with primary osteoporosis (n = 368) were allocated randomly to zoledronic acid plus loxoprofen (ZOL + LOX) or zoledronic acid alone (ZOL). All patients received 5-mg zoledronic acid infusion on day 1, and patients in the ZOL + LOX group also received 120 mg and 180 mg of oral loxoprofen on days 1 and 2, respectively. Adverse events and body temperature were recorded during the 7-day observation period.

Results

The incidence rates of APRs were 34.4% (64/186 patients) and 47.8% (87/182 patients) in the ZOL + LOX and ZOL groups, respectively (P = 0.0109). The proportions of patients with increased body temperature (≥ 1 °C and ≥ 37.5 °C) were similar in both groups (P = 0.1186). Past bisphosphonate users had a significantly lower incidence rate of APRs than treatment-naïve patients (odds ratio 0.444, 95% confidence interval 0.285–0.692, P = 0.0003).

Conclusions

Zoledronic acid-induced APRs appeared to be suppressed by loxoprofen. Known risk/protective factors, including prior osteoporosis treatment, were applicable to Japanese patients.

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Acknowledgements

This study was supported by the Comprehensive Support Project for Life-related Disease (CSP-LD) of the Public Health Research Foundation. The research fund was provided to CSP-LD by Asahi Kasei Pharma Corp. Asahi Kasei Pharma Corp. and CSP-LD took no part in this study other than providing information relevant to proper use of the study drug. All decisions concerning the planning and implementation of this study were made by the executive committee of this study.

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Authors and Affiliations

  1. Okimoto Clinic, 185-4 Kubi, Yutaka-machi, Kure, Hiroshima, 734-0304, Japan

    Nobukazu Okimoto

  2. Department of Orthopedic Surgery, School of Medicine, University of Occupational and Environmental Health, Fukuoka, 807-8555, Japan

    Akinori Sakai & Kunitaka Menuki

  3. Department of Orthopedic Surgery, Shimura Hospital, 3-13 Funairimachi, Naka-ku, Hiroshima, 730-0841, Japan

    Toru Yoshioka, Tomohiro Kobayashi & Kei Asano

  4. Department of Orthopedic Surgery, Obase Hospital, 1598 Aratsu, Kandamachi, Miyako, Fukuoka, 800-0344, Japan

    Shojiro Akahoshi, Toru Ishikura & Shito Fukuhara

  5. Department of Orthopedic Surgery, Saka Midorii Hospital, 6-28-1 Midorii, Asaminami-ku, Hiroshima, 731-0103, Japan

    Yoshifumi Fuse

  6. Department of Orthopedic Surgery, Shobara Red Cross Hospital, 2-7-10 Nishihonmachi, Shobara, Hiroshima, 727-0013, Japan

    Toshiyuki Mizuno

  7. Department of Orthopedic Surgery, Akaike Kyodo Clinic, 521Akaike, Fukuchimachi, Tagawa, Fukuoka, 822-1101, Japan

    Yuji Katae

  8. Department of Orthopedic Surgery, Sanzai Hospital, 3378 Shimosanzai, Saito, Miyazaki, 881-0113, Japan

    Hidehiro Matsumoto

  9. Department of Orthopedic Surgery, Kaisei General Hospital, 3-5-28 Muromachi, Sakaide, Kagawa, 762-0007, Japan

    Takayuki Ogawa

  10. Department of Orthopedic Surgery, Shin-Kokura Hospital, 1-3-1 Kanada, Kokurakita-ku, Kitakyushu, Fukuoka, 803-8505, Japan

    Shigeki Nishida

  11. Department of Orthopedic Surgery, Ken-Ai Memorial Hospital, 1191 Kimori, Onga-cho, Onga, Fukuoka, 811-4313, Japan

    Satoshi Ikeda

  12. Department of Orthopedic Surgery, Shunankogen Hospital, 29-1 Susumahongo, Shunan, Yamaguchi, 745-0122, Japan

    Jun Saito

  13. Department of Orthopedic Surgery, Tobata General Hospital, 1-3-33 Fukuryugi, Tobata, Kitakyushu, Fukuoka, 804-0025, Japan

    Yuichi Okazaki

  14. Department of Orthopedic Surgery, Saiseikai Kure Hospital, 2-1-13 Sanjyo, Kure, Hiroshima, 737-0821, Japan

    Naoyuki Mizuno

  15. Department of Pharmacy, Yasuda Women’s University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima, 731-0153, Japan

    Saeko Fujiwara

Authors
  1. Nobukazu Okimoto
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  2. Akinori Sakai
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  3. Toru Yoshioka
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  4. Tomohiro Kobayashi
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  5. Kei Asano
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  6. Shojiro Akahoshi
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  7. Toru Ishikura
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  8. Shito Fukuhara
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  9. Yoshifumi Fuse
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  10. Toshiyuki Mizuno
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  11. Yuji Katae
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  12. Hidehiro Matsumoto
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  13. Takayuki Ogawa
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  14. Shigeki Nishida
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  15. Satoshi Ikeda
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  16. Kunitaka Menuki
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  17. Jun Saito
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  18. Yuichi Okazaki
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  19. Naoyuki Mizuno
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  20. Saeko Fujiwara
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Corresponding author

Correspondence to Nobukazu Okimoto.

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Conflict of interest

N Okimoto has received grants from Asahi-Kasei Pharmaceutical Co., Ltd., during the conduct of the study; personal fees from Asahi-Kasei Pharmaceutical Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Daiichi-Sankyo Co. Ltd., Eisai Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Ono Pharmaceutical Co., Pfizer Japan Inc., Shionogi & Co., Ltd., Kaken Pharmaceutical Co. Ltd., Hisamitsu Pharmaceutical Co, Inc. and Teijin Pharma Ltd., outside the submitted work. A. Sakai has received grants from Asahi-Kasei Pharmaceutical Co., Ltd., during the conduct of the study; grants and personal fees from Asahi Kasei Pharma Corporation, Daiichi Sankyo Co., Ltd., and Chugai Pharmaceutical Co., Ltd., personal fees from Taisho Toyama Pharmaceutical Co., Ltd., outside the submitted work. S. Ikeda has received grants from Asahi-Kasei Pharmaceutical Co., Ltd., during the conduct of the study; Chugai Pharmaceutical Co., Daiichi-Sankyo Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co. and Teijin Pharma Ltd., outside the submitted work. T. Yoshioka, T. Kobayashi, K. Asano, S. Akahoshi, T. Ishikura, S. Fukuhara, Y. Fuse, T. Mizuno, Y. Katae, H. Matsumoto, T. Ogawa, S. Nishida, K. Menuki, J. Saito, Y. Okazaki and N. Mizuno received grants from Asahi-Kasei Pharmaceutical Co., Ltd. S. Fujiwara declares she has no conflict of interest.

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Okimoto, N., Sakai, A., Yoshioka, T. et al. Efficacy of non-steroidal anti-inflammatory drugs on zoledronic acid-induced acute-phase reactions: randomized, open-label, Japanese OZ study. J Bone Miner Metab 38, 230–239 (2020). https://doi.org/10.1007/s00774-019-01050-8

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  • DOI: https://doi.org/10.1007/s00774-019-01050-8

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