Low back pain (LBP) is a large problem in the general population and especially among people with a lower-limb amputation (LLA). The primary causes of LBP for people with LLA are whole-body kinematic and muscle asymmetries [1]. However, the sources of LBP are known to exist at the tissue-level such as within the intervertebral discs or facet joint capsules [2]. No previous study has identified the connection between determining the source of pain at the tissue-level and the cause of pain at the whole-body level. Identification of this interconnectivity is required for better understanding of LBP and therapeutic intervention for people with LLA. The purpose of this research was to create a multiscale model of the human lumbar spine in order to help identify and characterize the interconnectivity between wholebody biomechanics and tissue-level metrics leading to LBP for LLA. The results revealed that people with LLA have greater tissue-level loads than able-bodied individuals and suggest that people with LLA may perform certain motions with a more consistent strategy as compared to people without an amputation. These findings help to improve the current understanding of multiscale lumbar spine biomechanics, elucidate the greater risk for LBP in people with LLA, and can help to inform future treatment for biomechanical LBP.