Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude
Introduction
Extremely low-magnitude (<10 microstrain (με)), high frequency (10–100 Hz) mechanical signals, introduced to the skeleton using whole body vibration (WBV) can be anabolic to bone tissue, contributing to a skeletal structure that is less prone to fracture (Judex et al., 2003; Rubin et al., 2001a; Ward et al., 2004; Jankovich, 1972; Flieger et al., 1998; Tanaka et al., 2003). These mechanical signals can be orders of magnitude below those more typically considered in conjunction with exercise or applied loading regimens (Rubin and Lanyon, 1985; Turner et al., 1994), and thus may present a non-pharmacologic means of preventing/reversing osteoporosis without putting the skeleton at risk of damage. Despite this promising potential, few studies have investigated whether vibrations can prevent the changes in bone formation/resorption and the deterioration of bone morphology induced by a catabolic stimulus.
In postmenopausal women, WBV applied at magnitudes exceeding 5 g were able to increase hip bone mineral density (BMD) (Verschueren et al., 2004) while a similar WBV intervention, but with peak (vibration) accelerations reduced by an order of magnitude, prevented the decline in BMD in regions of the femoral neck and spine (Rubin et al., 2004a). Children suffering from cerebral palsy (Ward et al., 2004) and rodents subjected to disuse may also benefit from this extremely low-level mechanical countermeasure (Rubin et al., 2001b).
The degree by which variations in the parameters defining a WBV intervention, such as acceleration magnitude, frequency, or duration, alter the efficacy of the low-level mechanical signals is largely unknown. In the ovariectomized (OVX) rat, vibrations applied at either 17 Hz (0.5 g), 30 Hz (1.5 g), or 45 Hz (3 g) were all sensed in cortical bone but the signal at the highest frequency (and acceleration magnitude) was most effective in enhancing cellular activity and was the only one that prevented the loss of cortical bone strength (Oxlund et al., 2003). If bone indeed has a preference towards certain vibration frequencies and/or accelerations, the specific mechanical parameters modulating this different sensitivity have not been identified.
Considering the distinction between the relatively infrequent, but large magnitude locomotory strain signals and the omnipresent, but low-level mechanical signals that persist through actions such as standing, it is possible that the manner of the adaptive response to low-magnitude mechanical regimens does not follow the adaptive rules defined by factors such as longitudinal normal strain (Rubin and Lanyon, 1985; Turner et al., 1994), strain rate (O’Connor et al., 1982; Lamothe et al., 2005), or strain gradients (Judex et al., 1997; Gross et al., 1997), and that other loading characteristics, including the frequency of the signal or the number of loading cycles, play a more important role at these smaller magnitudes.
In an effort towards the development and optimization of WBV-based regimes that can effectively prevent and counteract bone loss, here, we tested the hypothesis that under hormonal challenges, a 90 Hz mechanical signal can be more effective in stimulating bone's anabolic activity than a signal half its frequency and that this differential sensitivity is independent of the induced strain magnitude.
Section snippets
Experimental design
All experimental procedures were approved by Stony Brook's Institutional Animal Care and Use Committee. OVX retired breeders (Sprague–Dawley) were purchased (Charles River Laboratories Inc., Wilmington, MA) and subsequently subjected to low amplitude (0.15 g peak acceleration) WBV at either 45 Hz () or 90 Hz () for 10 min/day (5 d/wk), or served as age-matched (long-term) OVX controls (). All rats were received in a single shipment and were 6–8mo old (female rats are retired according to
Induced strain environment
In vivo strain data collected from the antero-medial surface of the proximal tibia showed that dynamic strain magnitudes induced at 90 Hz averaged 0.74±0.11 με, 65% smaller () than those induced at 45 Hz (2.12±0.42 με) (Fig. 1). Similarly, peak strain rates produced by the 90 Hz signal (194±38 με/s) were 38% () smaller than during 45 Hz vibrations (312±53 με/s). The average intra-trial CV was 21% for 45 Hz trials and 48% for 90 Hz trials. The average intra-animal CV, across the five trials,
Discussion
The hypothesis that extremely low-magnitude WBV can stimulate bone formation in the OVX rat was tested. Similar to previous studies in which vibratory stimuli positively influenced bone mass in post-menopausal women (Rubin et al., 2004a), the current data suggest that WBV can serve as an anabolic signal to a skeleton even upon the withdrawal of estrogen. The efficacy of the signal, however, was strongly dependent on the frequency of the applied signal. While WBV applied for 10 min/d at a
Acknowledgments
Support from the Whitaker Foundation (RG-02-0564) and NIAMS (AR-43498) is gratefully acknowledged. Technical assistance from Drs. Maria Squire and Russell Garman is greatly appreciated.
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