An osteoporotic fracture occurs approximately every three seconds. Worldwide, this sums to nearly 9 million annual fractures caused by osteoporosis—a systemic, degenerative skeletal disorder that is characterized by low bone mass and increased bone tissue fragility. Although the individual and economic burden of osteoporosis nearly outweighs that of most cancers and many chronic illnesses, the existing methods for treatment are insufficient and many who are at risk remain undiagnosed. To develop improved osteoporosis treatments, prevent osteoporotic fractures, and promote bone health throughout the aging process, it is imperative to understand bone biomechanical behavior and the factors contributing to bone mechanotransduction and adaptation. Consequently, the first objective for the presented research was to characterize the effects and interactions of mechanical stimulus and biochemical signaling activity on the modeling and remodeling response of bovine and human trabecular bone through the use of ex vivo organ culture. The second objective for the research was to simulate the mechanical behavior and dynamic remodeling response of bone tissue through the use of finite element analyses and analytical cell population models. Collectively, the presented research illustrated that bone modeling and remodeling can be affected by the amount and type of applied mechanical stimulus and biochemical exposure. In addition, the research showed that, despite current limitations, simulation and prediction of bone response to applied stimulus is feasible with additional development of existing models.