Multiple myeloma (MM) is a hematological malignancy characterized by infinite proliferation and diffusion of plasma cells. Multiple myeloma bone disease (MBD) is the most common complication of MM. More than 70% of MM patients have bone damage in the course of disease progression, which leads to the increase of bone-related events such as bone pain, osteolytic changes, and pathological fractures. Relevant studies have shown that the pathogenesis of MBD is related to the changes of related cell factors and signaling pathways. The research on related cell factors has also promoted the development of a series of targeted therapeutic drugs. In this review, we summarize the important cell factors involved in the pathogenesis of MBD and the progress of it clinical targeted therapy.