The intricate link between load environment and skeletal health is exemplified by the severe osteopenia that accompanies prolonged periods of immobilization, frequently referred to as disuse osteoporosis. Investigating the effects disuse has on the structural properties of bone provides a unique opportunity to better understand how mechanical loads influence the adaptation and maintenance of skeletal tissue. Here, we report results from an examination of multiple indicators of bone metabolism (e.g., mean osteon density, mean osteon size, bone mass, and bone area distribution) within the major long bones of individuals with distinct activity level differences. Results are based on a sample comprising two subjects that suffered from long-term quadriplegia and 28 individuals of comparable age that had full limb mobility. Although limited in sample size, our findings suggest bones associated with long-term disuse have lower osteon densities and larger osteon areas compared to individuals of normal mobility, reflecting dramatically lower remodeling rates potentially related to reduced strain levels. Moreover, immobilized skeletal elements demonstrate a reduced percentage of cortical area present resulting from endosteal resorption. Differences between mobility groups in the percentage of cortical area present and bone distribution of all skeletal elements, suggests bone modeling activity is negligible in the unloaded adult skeleton. Additional histomorphometric comparisons reveal potential intraskeletal differences in bone turnover rates suggesting remodeling rates are highest within the humeri and femora. Addition of more immobilized individuals in the future will allow for quantitative statistical analyses and greater consideration of human variation within and between individuals. Am J Phys Anthropol 2012. © 2012 Wiley Periodicals, Inc.