We originally established an advanced imaging system to visualize living bone tissues using intravital two-photon microscopy, and revealed the dynamics of osteoclastic bone resorption which was finely regulated by cell-cell contact with bone-forming osteoblasts. By means of this system, we could grasp the real mode of actions of active vitamin D and parathyroid hormone (PTH) on bone metabolism. Furthermore, intravital imaging revealed that various biologic DMARDs acted at specific therapeutic points during bone destruction, with different efficacies. This technique facilitates investigation of cellular dynamics in the physiology and pathogenesis of bone disorders in vivo, and would thus be useful for evaluating the efficacy of novel anti-bone resorptive drugs currently developed in the world.