Physiological effects of prolonged exposure to microgravity are a major concern when considering crew health and performance during an interplanetary mission. Among the most mission-critical of these deleterious effects are the changes to the skeletal system. Loss of bone mineral density (BMD) can be approximated for outbound and inbound transit portions of a human Mars mission. However, the effect of Martian gravity (0.38G) on the skeletal system is not well understood. This paper presents an experimental design to study bone demineralization of weight bearing bones during prolonged exposure to the skeletal unloading of microgravity and reduced gravity (0.38G) environments and its implications for a human Mars mission.