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

Abstract

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice.

Feasibility and tolerability of whole‐body, low‐intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study

“…Three previous studies performed on boys with DMD used a high‐intensity, side‐alternating vibration platform . These 3 studies aimed primarily to examine safety and tolerability of vibration training, and all found whole‐body vibration to be feasible and safe, similar to our study and consistent with our preclinical observations . Besides using a different platform, the earlier studies used a shorter duration of vibration training and a lower frequency of vibration.…”

“…We chose a 10‐minute duration of low‐intensity vibration training based on previous reports that low‐magnitude, high‐frequency, whole‐body vibration treatment for 10 min/day resulted in increases in both bone and muscle mass in young women with low bone mineral density . The vibration frequency delivered by the Marodyne LivMD plate, 30–90 H z , is similar to the frequency found to be safe and without deleterious effects on diseased muscle in an mdx mouse model of DMD . Recent data show that, although high‐intensity training induces muscle damage in mdx mice, low‐intensity training reduces the level of protein carbonylation, a marker of oxidative damage, and rescues the mdx phenotype .…”

“…Novotny et al . first investigated this approach in a preclinical study using the mdx mouse model for DMD . The mdx mice were subjected to low‐magnitude, whole‐body vibration at a frequency of 30–90 H z , based on our previous work that identified 45 H z as most effective at increasing the expression of osteogenic genes .…”

Avaliação não invasiva de modelos murinos para doenças musculares genéticas

“…Micro-CT studies of dystrophic mice have so far focused on the evaluation of bone structure and architecture, extracting information such as trabecular bone morphometry, cortical bone geometry and volumetric bone density (Novotny et al, 2011(Novotny et al, , 2014. The low-coefficient of X-ray attenuation of soft tissues, such as muscle, limits the visualization of internal details in CT or micro-CT images.…”

“…The development of high-resolution tomography (micro-CT) has permitted the acquisition of images from small animals. Mouse models for muscle dystrophies have already been studied with micro-CT, but the investigation were focused on the evaluation of bones, lung and airway alterations (Lopez et al, 2008;Novotny et al, 2011Novotny et al, , 2014. To our knowledge, the description of muscle alterations in mice with micro-CT was restricted to the identification of atrophy (Manske et al, 2010;Weber et al, 2012).…”