Osteoporosis is a common skeletal disease characterized by bone loss and subsequent increased risk of fragility fractures. Recent advances in our mechanistic understanding of molecular communications among osteoblasts, osteoclasts, and osteocytes give insight into the important roles of the canonical Wnt/β-catenin pathway and the RANK/RANKL/OPG pathway in the process of bone remodeling. Due to the translation of the canonical Wnt/β-catenin pathway and the RANK/RANKL/OPG pathway in the regulation of osteoblasts and osteoclasts, new targets have been studied in recent years, such as sclerostin and receptor activator of NF-κB ligand (RANKL). In this review, we first introduce the signaling pathways involved in interactions among osteoblasts, osteoclasts, and osteocytes. Next, we describe clinical trials of denosumab and romosozumab, which are monoclonal antibodies that target RANKL and sclerostin, respectively. We analyze the efficacy of these drugs and provide a profile for the management of osteoporosis.