title: Effect of whole-body vibration and insulin-like growth factor-I on muscle paralysis-induced bone degeneration after botulinum toxin injection in mice.
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.
authors.affiliation: Institute of Biomechanics and Orthopaedics, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany, niehoff@dshs-koeln.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Niehoff
authors.forename: Philipp
authors.initials: P
authors.lastname: Lechner
authors.forename: Oana
authors.initials: O
authors.lastname: Ratiu
authors.forename: Sven
authors.initials: S
authors.lastname: Reuter
authors.forename: Nina
authors.initials: N
authors.lastname: Hamann
authors.forename: Gert-Peter
authors.initials: GP
authors.lastname: Brüggemann
authors.forename: Eckhard
authors.initials: E
authors.lastname: Schönau
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Ralf
authors.initials: R
authors.lastname: Beccard
mesh_terms: D000818:Animals; D015992:Body Mass Index; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology; D001905:Botulinum Toxins / Q000009:adverse effects*; D005260:Female; D005684:Gait; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009133:Muscular Atrophy / Q000139:chemically induced / Q000503:physiopathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013314:Stress, Mechanical; D014057:Tomography, X-Ray Computed; D014732:Vibration
chemical_list: D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D001905:Botulinum Toxins