Long-term transfemoral (i.e., above-knee) prosthesis users are at an increased risk of developing secondary musculoskeletal conditions compared to the general able-bodied population. Significant resources have been devoted to the immediate rehabilitation needs of persons undergoing lower-limb amputation, but there needs to be greater consideration for the early identification and modification of potential risk factors responsible for long- term development of secondary health conditions such as knee osteoarthritis (OA), hip OA, osteoporosis/osteopenia, and low back pain. The etiology for the development of these conditions is not entirely known or understood, but in persons with unilateral amputations they are believed to relate to the asymmetries and gait deviations that are typically demonstrated and required to walk with a prosthesis. Surprisingly, there are no studies to date that have investigated or determined the relative risk of transfemoral prosthesis users for developing secondary physical conditions on the basis of gender. We believe that it is important to conduct a preliminary investigation to determine if female transfemoral prosthesis users are at an increased risk of developing secondary musculoskeletal conditions compared to their male counterparts. Therefore, the purpose of this pilot study is to investigate the relative risk of persons with unilateral lower limb amputation for the development of musculoskeletal pathologies due to long-term prosthesis use. Specifically, we will investigate kinematic and kinetic differences between male and female transfemoral prosthesis users and the relationship to increased prevalence of osteopenia, osteoarthritis, and hip, knee or back pain. Additionally, we will develop and administer a nation-wide survey to document indicators of secondary physical conditions. The specific aims of this project are: Aim 1?To analyze biomechanical gait variables that are indicative of musculoskeletal risks in unilateral, transfemoral prosthesis users. We will perform quantitative gait analyses on 10 female subjects and 10 male subjects. It is hypothesized that peak ground reaction forces will be higher on the sound limb for women than for men and that the external knee adduction moment magnitude and rate will also be increased. Aim 2?To determine the presence of musculoskeletal pathologies in unilateral, transfemoral prosthesis users. We will perform a DEXA scan of the hips and spine of the 20 subjects and an X-ray of the sound limb knee to examine any presence of osteopenia or osteoarthritis. It is hypothesized that there will be a greater presence of musculoskeletal pathologies in the female subjects than the male subjects. Aim 3?To obtain information on self-reported musculoskeletal pathologies in unilateral, lower limb prosthesis users. A comprehensive on-line survey will be developed and utilized to determine the prevalence and severity of musculoskeletal pathologies. It is hypothesized that transfemoral prosthesis users will have a higher incidence of musculoskeletal pathologies, falls and fractures than transtibial prosthesis users. Furthermore, it is hypothesized that female prosthesis users will have a higher incidence of secondary physical conditions associated with amputation and long-term prosthesis use when compared with male prosthesis users. These preliminary data could be used in the future as a rationale to conduct larger, more in-depth and focused studies to investigate gender specific differences associated with particular secondary physical conditions that arise from amputation and prosthesis use. To develop cost-effective prosthetic solutions that are gender specific, we first need to collect and analyze data that will support and justify these types of development efforts.