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Utilization of Mechanical Stress to Treat Osteoporosis: The Effects of Electrical Stimulation, Radial Extracorporeal Shock Wave, and Ultrasound on Experimental Osteoporosis in Ovariectomized Rats

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Abstract

Current treatment options for osteoporosis primarily involve pharmacotherapies, but they are often accompanied by undesirable side effects. Utilization of mechanical stress which can noninvasively induce bone formation has been suggested as an alternative to conventional treatments. Here, we examined the efficacy of mechanical stress induced by electrical stimulation, radial extracorporeal shock waves, and ultrasound for estrogen-deficient osteoporosis. Female Wistar rats were divided into following five groups: sham-operated group, untreated after ovariectomy, and treated with electrical stimulation, radial extracorporeal shock wave, or ultrasound starting at 8 weeks after ovariectomy for 4 weeks. Trabecular bone architecture of the femur was assessed by micro-CT and its biomechanical properties were obtained by mechanical testing. The femurs were further evaluated by histochemical, immunohistochemical, and real-time PCR analyses. Radial extracorporeal shock wave and ultrasound treatment improved trabecular bone microarchitecture and bone strength in osteoporotic rats, but not electrical stimulation. The shock wave decreased osteoclast activity and RANKL expression. The exposure of ultrasound increased osteoblast activity and β-catenin-positive cells, and they decreased sclerostin-positive osteocytes. These findings suggest that mechanical stress induced by radial extracorporeal shock wave and ultrasound can improve estrogen-deficient bone loss and bone fragility through promoted bone formation or attenuated bone resorption.

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Data Availability

The datasets used and analyzed during this study are available from corresponding author upon request.

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Acknowledgements

We thank Mr. Masato Nomura, Mr. Yoshio Wakimoto, Mr. Ryota Suzuki, Mr. Takumi Yakuwa, Mr. Changxin Li, Mr. Taisei Wakigawa, Mr. Toshiya Tsubaki, and Ms. Sae Kinoshita for their skilled technical assistance; Asst. Prof. Akira Ito and Dr. Akihiro Nakahata for their support with mechanical testing; and Asst. Prof. Noriaki Maeshige for support with the ultrasound transducer. We are also grateful to Nihon Medix Co., Ltd. for providing the electrical stimulator; and SAKAI Medical Co., Ltd. for providing the radial extracorporeal shock wave device.

Funding

This work was supported by the Japan Society for the Promotion of Science KAKENHI Grant No. 16K12933 and Suzuken Memorial Foundation.

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Authors and Affiliations

  1. Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan

    Shota Inoue & Junpei Hatakeyama

  2. OG Wellness Technologies Co., Ltd, Okayama, Japan

    Hitoshi Aoki

  3. Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Hiroshi Kuroki

  4. Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan

    Takahiro Niikura, Keisuke Oe, Tomoaki Fukui & Ryosuke Kuroda

  5. Life and Medical Sciences Area, Health Sciences Discipline, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, Hyogo, 654-0142, Japan

    Toshihiro Akisue & Hideki Moriyama

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  1. Shota Inoue
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Correspondence to Hideki Moriyama.

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Shota Inoue, Junpei Hatakeyama, Hitoshi Aoki, Hiroshi Kuroki, Takahiro Niikura, Keisuke Oe, Tomoaki Fukui, Ryosuke Kuroda, Toshihiro Akisue, and Hideki Moriyama declare that they have no conflict of interest.

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All experimental procedures were approved by the Institutional Animal Care and Use Committee and performed according to the Kobe University Animal Experimentation Regulations (approval number: P160607).

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Inoue, S., Hatakeyama, J., Aoki, H. et al. Utilization of Mechanical Stress to Treat Osteoporosis: The Effects of Electrical Stimulation, Radial Extracorporeal Shock Wave, and Ultrasound on Experimental Osteoporosis in Ovariectomized Rats. Calcif Tissue Int 109, 215–229 (2021). https://doi.org/10.1007/s00223-021-00831-6

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