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Effect of Whole-Body Vibration and Insulin-Like Growth Factor-I on Muscle Paralysis-Induced Bone Degeneration after Botulinum Toxin Injection in Mice

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Abstract

Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 μg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.

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Acknowledgments

The study was supported by Ipsen Pharma and Novotec Medical. Its sponsors had no involvement in the study design, collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Institute of Biomechanics and Orthopaedics, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany

    Anja Niehoff, Nina Hamann & Gert-Peter Brüggemann

  2. Cologne Center for Musculoskeletal Biomechanics, Medical Faculty, University of Cologne, Cologne, Germany

    Anja Niehoff

  3. Children’s Hospital, University of Cologne, Cologne, Germany

    Philipp Lechner, Oana Ratiu, Sven Reuter, Eckhard Schönau & Ralf Beccard

  4. Department of Molecular and Cellular Sport Medicine, Institute of Cardiology and Sport Medicine, German Sport University Cologne, Cologne, Germany

    Wilhelm Bloch

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Correspondence to Anja Niehoff.

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ES participates in advisory boards and gives presentations for different companies. Besides, none of the authors has anything to disclose for this manuscript and there are no conflicts of interest.

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Niehoff, A., Lechner, P., Ratiu, O. et al. Effect of Whole-Body Vibration and Insulin-Like Growth Factor-I on Muscle Paralysis-Induced Bone Degeneration after Botulinum Toxin Injection in Mice. Calcif Tissue Int 94, 373–383 (2014). https://doi.org/10.1007/s00223-013-9818-3

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