The skeleton's ability to withstand the extremes of physical activity is achieved in large part by its capacity to perceive and respond to small changes in its mechanical environment. Strains generated by functional activity would represent an efficient, epigenetic parameter by which the bone cell population could assess the skeleton's structural effectiveness, and subsequently use this information to influence its morphology. However, contrary to our normal interpretation of Wolff's Law, minimizing strain does not appear to be the paramount goal of adaptation, but rather skeletal morphology interacts with functional activity to generate a certain, perhaps cytologically beneficial, type of strain.

Three sections are used to address the epigenetic impact on bone morphology:​ (a) at the level of the organ, the strains generated by functional activity;​ (b) at the level of the tissue, osteoregulatory parameters of the strain environment;​ and (c) at the level of the cell, the mechanisms by which physical information is translated to an adaptive response. Only when we understand the mechanisms and objectives of tissue adaptation in the normal skeleton can our perspective and treatment of functionally influenced skeletal pathologies (e.g. osteopenias, fractures) be enhanced.