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Inhibitory effect of bisphosphonate on osteoclast function contributes to improved skeletal pain in ovariectomized mice

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Abstract

The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonate (BP) on pain in an ovariectomized (OVX) mouse model. We evaluated skeletal pain in OVX mice through an examination of pain-like behavior as well as immunohistochemical findings. In addition, we assessed the effects of alendronate (ALN), a potent osteoclast inhibitor, on those parameters. The OVX mice showed a decrease in the pain threshold value, and an increase in the number of c-Fos immunoreactive neurons in laminae I–II of the dorsal horn of the spinal cord. Alendronate caused an increase in the pain threshold value and inhibited c-Fos expression. The serum level of tartrate-resistant acid phosphatase 5b, a marker of osteoclast activity, was significantly negatively correlated with the pain threshold value. Furthermore, we found that an antagonist of the transient receptor potential channel vanilloid subfamily member 1, which is an acid-sensing nociceptor, improved pain-like behavior in OVX mice. These results indicated that the inhibitory effect of BP on osteoclast function might contribute to an improvement in skeletal pain in osteoporosis patients.

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Acknowledgments

We would like to thank Prof. Moriyama, Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan, for kindly providing the antibody to V-ATPase. This study was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and by a grant for scientific research from MSD K.K. (Tokyo, Japan).

Conflict of interest

All authors have no potential conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan

    Yasuhisa Abe, Kousuke Iba, Koichi Sasaki, Hironori Chiba, Kumiko Kanaya & Toshihiko Yamashita

  2. Department of Anesthesiology and Resuscitology, Shinsyu University School of Medicine, Matsumoto, Japan

    Tomoyuki Kawamata

  3. Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Kimimitsu Oda

  4. Department of Developmental Biology of Hard Tissue, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan

    Norio Amizuka & Muneteru Sasaki

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  1. Yasuhisa Abe
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  2. Kousuke Iba
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Correspondence to Kousuke Iba.

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Abe, Y., Iba, K., Sasaki, K. et al. Inhibitory effect of bisphosphonate on osteoclast function contributes to improved skeletal pain in ovariectomized mice. J Bone Miner Metab 33, 125–134 (2015). https://doi.org/10.1007/s00774-014-0574-x

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  • DOI: https://doi.org/10.1007/s00774-014-0574-x

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