Countermeasures that address the combined effects of simulated microgravity and ionizing radiation have not been investigated in bone. Both these factors are inherent to the spaceflight environment and thus, countermeasures must be investigated regarding their protective effect when both are in combination. We sought to evaluate the potentially differing effects of microgravity and ionizing radiation when controlled independently on bone and the two factors in combination. For the purpose of this study, we have used the hindlimb unloading model, in combination with exposure to total body irradiation (132Cs gamma radiation, at 2 Gy dose) as analogs of weightlessness and radiation exposure. The relatively higher dose of radiation (2 Gy) was chosen as a positive control dose to ensure bone loss in rodents to allow for testing DP as a countermeasure for bone loss. We sought to determine if the DP diet prevents simulated-microgravity induced bone loss (HU), as well as if the diet is also effective at preventing simulated spaceflight-induced bone loss (combination of HU+irradiation (IR). To address these questions, we analyzed both cancellous and cortical bone microarchitecture as well as bone quality. Additionally, we aimed to determine if the DP diet had the capacity to protect osteoprogenitors after exposure to simulated microgravity, an essential part in the healthy maintenance of the skeletal tissue.