Assessment of the in vivo adaptive response to mechanical loading

The primary responsibility of the skeleton is to bear the loads involved in physical activity without sustaining damage. This capability involves a mechanism in which bone cells "assess" the suitability of the bones' existing architecture in relation to their prevailing loading environment and adapt or maintain it accordingly. It is widely assumed that the loading-related variable to which the bone cells respond is the strain engendered within the bone tissue. Strain-related adaptation is essential for normal bone development, regulation of strength in relation to exercise, healing of fractures and the success of orthopedic interference. The most widespread failure of this adaptive response is osteoporosis. Although strain-related bone adaptation can be investigated in these situations in humans in vivo, both the inputs and outputs are difficult to assess and control, and the tissues are unavailable for study. As a consequence much of our understanding of the mechanisms involved in strain-related adaptation have come from studies in animals where the strains within the bone are measured, the loads imposed on the bones can be controlled, and the adaptive changes to cells and architecture determined. Although many animals have been used in the past (1-3), now the most commonly used animal is the mouse. Normal and transgenic mice are available and inbred strains of mice are well characterized physiologically (4). Most importantly, the techniques for measuring strains in mouse bones, loading these bones in a controlled manner, and assessing changes in architecture are all available. This chapter outlines the techniques involved in these three phases of investigation in mouse bone.