A prospective study of human bone adaptation using a novel in-vivo loading model

Abstract Although it is understood that mechanical stimuli initiate bone adaptation, the exact manner in which bone structure and strength adapt in response to specific aspects of a mechanical signal, such as strain magnitude, has not been prospectively studied in humans. It is likely that human bone behaves in a fundamentally similar manner to animal bone, but the details of how this occurs may differ between species. For example, the relative proportions of cortical and trabecular bone tissue and differences in available surface area and surface to volume ratio differ substantially between small animals and humans. These differences may cause specific mechanical signal characteristics have differing relative importance in humans versus small animals. Similarly, different strain magnitudes may be required to initiate an osteogenic response in humans. This knowledge is fundamental for optimizing exercise interventions to prevent or slow the loss of bone strength that can lead to osteoporosis and fractures. The long-term goal of this research is to understand how human bone structure and strength are modified in response to different mechanical stimuli. The purpose of this project is to quantitatively define the relationships between loading exposure and adaptive changes to distal radius bone structure and strength in women, to determine how these relationships are mediated by physical activity, initial bone status, and muscle function, and to measure the changes to bone after a mechanical stimulus is withdrawn. This will be accomplished with a human in vivo loading model developed and validated by the PI. One hundred twenty subjects will participate in this clinical research study. Those randomized to experimental groups will participate in a 12 month distal radius mechanical loading regime to prospectively link mechanical loading environment with bone adaptation. Aim 1: Quantify the effect of strain magnitude on 12-month changes to cortical and trabecular bone quantity, structure and strength at the distal radius. Aim 2: Quantify the effect of strain rate on 12-month changes to cortical and trabecular bone quantity, structure and strength at the distal radius. Aim 3: Determine the influence of initial bone status, bone loading physical activity, and muscle function on the strain/adaptive response relationship. Aim 4: Quantify the degree to which changes in bone structure and strength are preserved during a 12-month follow-up period. The contribution of the research is expected to be an improved understanding of how human bone structure and strength are modified in response to changes in mechanical loading environment. The research will also identify the degree to which bone adaptation is dependent upon initial bone status, physical activity levels, and muscle function. This is significant because it will establish a quantitative basis for the development and evaluation of optimized exercise strategies that will prevent or slow the loss of bone strength that can lead to fractures and osteoporosis, and will provide a basis for prospectively identifying those individuals who may most benefit from these strategies.