Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude

Abstract

There is growing evidence that extremely small mechanical signals, if applied at a sufficiently high frequency, can serve as anabolic signals to bone tissue. To determine if the responsiveness of bone to low-magnitude, high-frequency parameters is modulated by endocrine imbalance, ovariectomized (OVX) Sprague–Dawley rats were subjected to whole body vibrations (WBV, 0.15 g) at 45 Hz ($n=6$) or 90 Hz ($n=6$) for 10 min/day, and compared to OVX age-matched controls ($n=6$). Five additional rats were used, in vivo, to establish the induced bone surface strain magnitudes (and strain rates). Following a 28 d protocol, bone formation rates in the metaphysis of the proximal tibia were 159% greater in 90 Hz rats when compared to age-matched controls, but 45 Hz rats were not significantly different from controls. Bone morphology of 90 Hz rats indicated significantly greater trabecular bone volume (22% and 25%) and thicker trabeculae (11% and 12%) over either controls or 45 Hz rats in the epiphysis of the distal femur, respectively. Despite the enhanced sensitivity of the skeleton towards the 90 Hz signal, the strain magnitudes and strain rates induced by this frequency were significantly lower than during 45 Hz vibration, suggesting that factors other than matrix strain are driving the anabolic response. Ideally, such mechanical signals represent a non-pharmacologic means of controlling bone mass and morphology in spite of systemic pressures for bone resorption.

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.