Approximately 1 in 4 patients with advanced breast cancer develop incurable skeletal metastasis, which is the leading cause of breast cancer-related deaths among women worldwide. Breast cancer metastasis is overwhelmingly osteolytic, causing increased bone fragility and fracture. This bone loss occurs because metastatic cancer cells dysregulate the normal bone turnover process in order to release pro-tumorigenic factors that are stored within the skeletal matrix. Normal bone turnover of the skeleton balances resorption and formation to meet the structural and metabolic needs of bone via a feedback loop that is regulated by the prevailing mechanical environment, which develops from everyday activities as walking, exercise, or sitting. This talk will discuss novel models of human metastatic bone cancer with applied mechanical loading used for investigating the effects of mechanical loading, well as preliminary work indicating that modulating the mechanical environment, specifically increasing the stimuli, plays an inhibitory role in this context.