Is bone formation induced by high-frequency mechanical signals modulated by muscle activity?

Abstract

Bone formation and resorption are sensitive to both external loads arising from gravitational loading as well to internal loads generated by muscular activity. The question as to which of the two sources provides the dominant stimulus for bone homeostasis and new bone accretion is arguably tied to the specific type of activity and anatomical site but it is often assumed that, because of their purportedly greater magnitude, muscle loads modulate changes in bone morphology. High-frequency mechanical signals may provide benefits at low- (<1g) and high- (>1g) acceleration magnitudes. While the mechanisms by which cells perceive high-frequency signals are largely unknown, higher magnitude vibrations can cause large muscle loads and may therefore be sensed by pathways similar to those associated with exercise. Here, we review experimental data to examine whether vibrations applied at very low magnitudes may be sensed directly by transmittance of the signal through the skeleton or whether muscle activity modulates, and perhaps amplifies, the externally applied mechanical stimulus. Current data indicate that the anabolic and anti-catabolic effects of whole body vibrations on the skeleton are unlikely to require muscular activity to become effective. Even high-frequency signals that induce bone matrix deformations of far less than five microstrain can promote bone formation in the absence of muscular activity. This independence of cells on large strains suggests that mechanical interventions can be designed that are both safe and effective.

Figure 1

Three different pathways by which mechanical signals produced during whole body vibrations may be sensed by cells within a bone of the appendicular skeleton. Cells that may convert the mechanical signal into biochemical language include osteoblasts/osteoclasts/lining-cells on bone surfaces, osteocytes within the calcified matrix, and mesenchymal precursors within the bone marrow.

Figure 2

Upon application of low-level (0.3g) whole-body vibrations for 15min/d, differences in cross-sectional muscle area of the soleus were readily available after 6wk. The ratio between type I (slow, stained black) and type II (fast, stained white) muscle fibers remained unchanged by the mechanical intervention.

Figure 3

With the anesthetized mouse in a supine position, the tibia can be readily subjected to high-frequency horizontal sinusoidal motions produced by a linear actuator (top panel). Even a brief daily exposure to this mechanical signal in the absence of muscle tone can produce skeletal benefits such as greater trabecular bone volume fraction and greater trabecular connected in the metaphysis of the tibia.

Figure 4

Activity levels and energy expenditure assessed by indirect calorimetry nine weeks into an experimental protocol during which mice were subjected to 15min/d, of low-level whole-body vibrations (90Hz, 0.2g) or allowed to freely roam their cages.