Osteoporosis is a bone disease that poses a tremendous burden to health care. The receptor activator of nuclear factor-KB (RANK) and its ligand (RANKL) have been a major focus of this research field. RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also adjusts bone homeostasis both in normal physiology and in bone disease. Consequently, novel drugs specifically targeting RANK-RANKL and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various bone diseases such as osteoporosis. Osteoclasts are the exclusive cells involved in bone resorption. Abnormal activation of osteoclasts can lead to reduced bone density, resulting in osteopenia, osteoporosis and other bone disorders. To date, the mechanism of how osteoclast precursors differentiate into mature osteoclasts remains elusive. Cell proliferation and cell death may be key processes in the progression as well as other cell types. Oncogene products and tumor-suppressor molecules play a pivotal role in regulating the processes, which are important in regulating the configuration of bone disorders. Based on the understanding of these processes, promising alternatives to the use of medications against osteoporosis include specific diets with plant-derived supplements to modulate the expression and/or activity of these molecules. In this review, we summarize the progress of research with a focus on the modulatory roles of oncogene products and tumor-suppressor molecules and suggest the scope of further research concerning the prevention of osteoporosis in this field.