Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation. J Orthop Res

Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794-2580, USA.
Journal of Orthopaedic Research (Impact Factor: 2.97). 06/2007; 25(6):732-40. DOI: 10.1002/jor.20354
Source: PubMed

ABSTRACT High-frequency whole body vibrations can be osteogenic, but their efficacy appears limited to skeletal segments that are weight bearing and thus subject to the induced load. To determine the anabolic component of this signal, we investigated whether low-level oscillatory displacements, in the absence of weight bearing, are anabolic to skeletal tissue. A loading apparatus, developed to shake specific segments of the murine skeleton without the direct application of deformations to the tissue, was used to subject the left tibia of eight anesthesized adult female C57BL/6J mice to small (0.3 g or 0.6 g) 45 Hz sinusoidal accelerations for 10 min/day, while the right tibia served as an internal control. Video and strain analysis revealed that motions of the apparatus and tibia were well coupled, inducing dynamic cortical deformations of less than three microstrain. After 3 weeks, trabecular metaphyseal bone formation rates and the percentage of mineralizing surfaces (MS/BS) were 88% and 64% greater (p < 0.05) in tibiae accelerated at 0.3 g than in their contralateral controls. At 0.6 g, bone formation rates and mineral apposition rates were 66% and 22% greater (p < 0.05) in accelerated tibiae. Changes in bone morphology were evident only in the epiphysis, where stimulated tibiae displayed significantly greater cortical area (+8%) and thickness (+8%). These results suggest that tiny acceleratory motions--independent of direct loading of the matrix--can influence bone formation and bone morphology. If confirmed by clinical studies, the unique nature of the signal may ultimately facilitate the stimulation of skeletal regions that are prone to osteoporosis even in patients that are suffering from confinement to wheelchairs, bed rest, or space travel.

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Available from: Clinton Rubin, Aug 17, 2015
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    • "MicroCT distinguishes itself from other imaging techniques in its ability to acquire high-resolution images based on the physical density of the tissue. Because of the much greater density of calcified tissue, this technique has been used extensively in biomedical research to quantify the morphology and micro-architecture of the skeleton [14] [15] [16]. However, microCT also provides a three-dimensional density map with sufficiently large density gradients (contrast) to distinguish adipose tissue from other tissues, fluids, and cavities without contrast agents. "
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    • "In vivo, extracellular matrix strains generated by low-level vibrations are at least two orders of magnitude smaller than those required to elicit a response when the signal frequency is much lower (Xie et al., 2006). Not only are vibration induced matrix deformations small but, unlike strains engendered by low-frequency mechanical signals, they are also not directly related to osteogenesis (Garman et al., 2007). An alternative parameter, fluid shear, can alter transcriptional activity at laminar (Ponik and Pavalko, 2004), pulsatile (Mullender et al., 2006) and oscillating (Donahue et al., 2003) low-frequency (o15 Hz) conditions. "
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    ABSTRACT: Consistent across studies in humans, animals and cells, the application of vibrations can be anabolic and/or anti-catabolic to bone. The physical mechanisms modulating the vibration-induced response have not been identified. Recently, we developed an in vitro model in which candidate parameters including acceleration magnitude and fluid shear can be controlled independently during vibrations. Here, we hypothesized that vibration induced fluid shear does not modulate mesenchymal stem cell (MSC) proliferation and mineralization and that cell's sensitivity to vibrations can be promoted via actin stress fiber formation. Adipose derived human MSCs were subjected to vibration frequencies and acceleration magnitudes that induced fluid shear stress ranging from 0.04Pa to 5Pa. Vibrations were applied at magnitudes of 0.15g, 1g, and 2g using frequencies of both 100Hz and 30Hz. After 14d and under low fluid shear conditions associated with 100Hz oscillations, mineralization was greater in all vibrated groups than in controls. Greater levels of fluid shear produced by 30Hz vibrations enhanced mineralization only in the 2g group. Over 3d, vibrations led to the greatest increase in total cell number with the frequency/acceleration combination that induced the smallest level of fluid shear. Acute experiments showed that actin remodeling was necessary for early mechanical up-regulation of RUNX-2 mRNA levels. During osteogenic differentiation, mechanically induced up-regulation of actin remodeling genes including Wiskott-Aldrich syndrome (WAS) protein, a critical regulator of Arp2/3 complex, was related to the magnitude of the applied acceleration but not to fluid shear. These data demonstrate that fluid shear does not regulate vibration induced proliferation and mineralization and that cytoskeletal remodeling activity may play a role in MSC mechanosensitivity.
    Journal of Biomechanics 07/2013; 46(13). DOI:10.1016/j.jbiomech.2013.06.008 · 2.50 Impact Factor
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    • "To the best of our knowledge, we are the first to identify an overall bone gain to such conditions in male mature rats. In this group, we also found that tibia resorption activity was unaffected, in contrast to what was found in young [42] or adult [43] female mice and in an in vitro study [13]. Overall, the positive results of the 90 Hz group suggested that some components in the bone tissue itself are sensitive to higher frequencies than those corresponding to muscle resonant frequencies. "
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    ABSTRACT: Whole body vibration (WBV) is receiving increasing interest as an anti-osteoporotic prevention strategy. In this context, selective effects of different frequency and acceleration magnitude modalities on musculoskeletal responses need to be better defined. Our aim was to investigate the bone effects of different vibration frequencies at constant g level. Vertical WBV was delivered at 0.7g (Peak acceleration) and 8, 52 or 90 Hz sinusoidal vibration to mature male rats 10 minutes daily for 5 days/week for 4 weeks. Peak accelerations measured by skin or bone-mounted accelerometers at L2 vertebral and tibia crest levels revealed similar values between adjacent skin and bone sites. Local accelerations were greater at 8 Hz compared to 52 and 90 Hz and were greater in vertebra than tibia for all the frequencies tested. At 52 Hz, bone responses were mainly seen in L2 vertebral body and were characterized by trabecular reorganisation and stimulated mineral apposition rate (MAR) without any bone volume alteration. At 90 Hz, axial and appendicular skeletons were affected as were the cortical and trabecular compartments. Cortical thickness increased in femur diaphysis (17%) along with decreased porosity; trabecular bone volume increased at distal femur metaphysis (23%) and even more at L2 vertebral body (32%), along with decreased SMI and increased trabecular connectivity. Trabecular thickness increased at the tibia proximal metaphysis. Bone cellular activities indicated a greater bone formation rate, which was more pronounced at vertebra (300%) than at long bone (33%). Active bone resorption surfaces were unaffected. At 8 Hz, however, hyperosteoidosis with reduced MAR along with increased resorption surfaces occurred in the tibia; hyperosteoidosis and trend towards decreased MAR was also seen in L2 vertebra. Trabecular bone mineral density was decreased at femur and tibia. Thus the most favourable regimen is 90Hz, while deleterious effects were seen at 8 Hz. We concluded that the skeleton is frequency-scalable, thus highlighting the importance of WBV regimen conditions and suggesting that cautions are required for frequencies less than 10 Hz, at least in rats.
    Bone 03/2013; 55(1). DOI:10.1016/j.bone.2013.03.013 · 4.46 Impact Factor
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