The skeleton in a physical world.

All organisms exist within a physical space and respond to physical forces as part of daily life. In higher organisms, the skeleton is critical for locomotion in the physical environment, providing a carapace upon which the animal can move to accomplish functions necessary for living. As such, the skeleton has responded evolutionarily, and does in real-time, to physical stresses placed on it to ensure that its structure supports its function in the sea, in the air, and on dry land. In this article, we consider how those cells responsible for remodeling skeletal structure respond to mechanical force including load magnitude, frequency, and cyclicity, and how force rearranges cellular structure in turn. The effects of these forces to balance the mesenchymal stem cell supply of bone-forming osteoblasts and energy storing adipocytes are addressed. That this phenotypic switching is achieved at the level of both gene transactivation and alteration of structural epigenetic controls of gene expression is considered. Finally, as clinicians, we consider this information as it applies to a prescriptive for intelligent exercise.