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Mechanical Stress by Spasticity Accelerates Fracture Healing After Spinal Cord Injury

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Abstract

Accelerated fracture healing in patients with spinal cord injuries (SCI) is often encountered in clinical practice. However, there is no distinct evidence in the accelerated fracture healing, and the mechanisms of accelerated fracture healing in SCI are poorly understood. We aimed to determine whether SCI accelerated fracture healing in morphology and strength, to characterize the healing process with SCI, and to clarify the factors responsible for accelerated fracture healing. In total, 39 male Wistar rats were randomly divided into healthy control without intervention, SCI only, fracture with SCI, botulinum toxin (BTX) A-treated fracture with SCI, and propranolol-treated fracture with SCI groups. These rats were assessed with computed microtomography, histological, histomorphological, immunohistological, and biomechanical analyses. Both computed microtomography and histological analyses revealed the acceleration of a bony union in animals with SCI. The strength of the healed fractures after SCI recovered to the same level as that of intact bones after SCI, while the healed bones were weaker than the intact bones. Immunohistology revealed that SCI fracture healing was characterized by formation of callus with predominant intramembranous ossification and promoting endochondral ossification. The accelerated fracture healing after SCI was attenuated by BTX injection, but did not change by propranolol. We demonstrated that SCI accelerate fracture healing in both morphology and strength. The accelerated fracture healing with SCI may be due to predominant intramembranous ossification and promoting endochondral ossification. In addition, our results also suggest that muscle contraction by spasticity accelerates fracture healing after SCI.

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Acknowledgements

We would like to thank Daichi Watanabe and Kousuke Watanabe for animal care. We are also grateful to Daisuke Inoue, Akira Ito, and Hiroki Iijima for their support with mechanical testing. The synchrotron radiation experiments were performed at the BL20B2 of Spring-8 with the approval of the Japan Synchrotron Radiation Research Institute (JASRI) (Proposal No. 2014A1681). This study was supported by Grant-in-Aid for Challenging Exploratory Research (25560260) from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, Hyogo, 654-0142, Japan

    Naoyoshi Sakitani, Hiroyuki Iwasawa, Masato Nomura & Yasushi Miura

  2. St. Marianna University School of Medicine Hospital, Sugao 2-16-1, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan

    Hiroyuki Iwasawa

  3. Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, Syogoinkawaharatyo 53, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan

    Hiroshi Kuroki

  4. Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, 739-2695, Japan

    Junya Ozawa

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

    Hideki Moriyama

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  1. Naoyoshi Sakitani
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Contributions

Conception and design on the study: HM. Acquisition of the data: NS, HI, and MN. Analysis and interpretation of the data: NS, YM, JO, and HM. Drafting the article: NS, HK, JO, and HM. Technical support: YM, HK, and JO. Critical revision of the article for important intellectual content: NS, HI, MN, YM, HK, JO, and HM. All authors read and approved the final manuscript.

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Correspondence to Hideki Moriyama.

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Naoyoshi Sakitani, Hiroyuki Iwasawa, Masato Nomura, Yasushi Miura, Hiroshi Kuroki, Junya Ozawa and Hideki Moriyama certifies that he or a member of his immediate family, has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with submitted article.

Human and Animal Rights and Informed Consent

All applicable international, national, and/or institutional guidelines for the care and use of animal were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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223_2017_293_MOESM1_ESM.eps

Supplementary material 1 (EPS 1430 kb). Fig. 1 Study design with the assignment of animals to each group and the timeline of analyses.

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Sakitani, N., Iwasawa, H., Nomura, M. et al. Mechanical Stress by Spasticity Accelerates Fracture Healing After Spinal Cord Injury. Calcif Tissue Int 101, 384–395 (2017). https://doi.org/10.1007/s00223-017-0293-0

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