High-Frequency, Low-Magnitude Vibration Does Not Prevent Bone Loss Resulting from Muscle Disuse in Mice following Botulinum Toxin Injection

Abstract

High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB) would maintain bone in a muscle disuse model with botulinum toxin type A (BTX). Female 16–18 wk old BALB/c mice (N = 36) were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass) into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ±0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA) and tibial bone properties (epiphysis, metaphysis and diaphysis) were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12±9% and 7±6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

Immobilization induced osteopenia is strain specific in mice

“…These findings are consistent with previous studies investigating BTX-induced immobilization in both mice and rats, and validate the reproducibility of the BTX-induced immobilization model in mice (Warner et al, 2006a, Warden et al, 2013, Brüel et al, 2013, Ellman et al, 2014, Manske et al, 2010a, Aliprantis et al, 2012, Grimston et al, 2007, Manske et al, 2010b, Manske et al, 2012, Poliachik et al, 2010). …”

“…We have previously shown losses of bone density, microstructure, and strength in rats following BTX injection (Vegger et al, 2014, Thomsen et al, 2012, Brüel et al, 2013, Grubbe et al, 2014), and these findings are similar to what has been shown in mice (Warner et al, 2006a, Warden et al, 2013, Ellman et al, 2014, Manske et al, 2010a, Aliprantis et al, 2012, Grimston et al, 2007, Ausk et al, 2013, Manske et al, 2010b, Manske et al, 2012, Poliachik et al, 2010, Warner et al, 2006b). Furthermore, it has been demonstrated that the bone deterioration following BTX-induced muscle paralysis is paralleled by an increase in osteoclast activity and osteoclastogenesis, and these two factors are believed to play key roles for the rapidly occurring bone loss in this model of immobilization (Aliprantis et al, 2012, Warner et al, 2006b).…”

Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

“…The vibration training protocol used in the present study did not improve muscle size or strength in mdx or wildtype mice. The lack of vibration-induced improvements in muscle is consistent with results from another study that used botulism toxin to induce muscle weakness [41], but contradicts our previous vibration work in wildtype mice in which muscle strength improved by 10% despite no effect on muscle mass, size, or protein content [50]. Of interest, our previous study on wildtype mice was conducted using the same vibration device except that the vibration parameters were slightly different (1.0 g and 45 Hz) and the device was placed on a bench top [50].…”

High-Frequency Vibration Treatment of Human Bone Marrow Stromal Cells Increases Differentiation toward Bone Tissue

“…Vibrations, transmitted along the body during locomotion, are responsible for maintaining posture, muscle tone, and bone remodeling, and recently their effectiveness in some murine models of bone disease has been demonstrated [71, 72]. Nevertheless, in vivo results remain controversial, as important variables, like nutrition and genetic make-up, may impact response to HFV stimulation.…”