A major disadvantage of a systemic VDR-null mouse model is that the expected 1,25 dihydroxy vitamin D [1,25(OH)_2D] -mediated skeletal and renal adaptations to reduced intestinal calcium absorption do not occur, due to the lack of VDR activity in these tissues. Systemic VDR-null mice, therefore, are not an appropriate model to unravel the physiological repercussions of negative calcium balance (or lack of intestinal 1,25(OH)_2D activity) on calcium and bone homeostasis. Accordingly, we have generated tissue specific VDR-ablation to manipulate local 1,25(OH)_2D activity. Furthermore, calcium movement from bone after osteoclastic bone resorption is a large calcium supply to maintain calcium homeostasis, the system supporting calcium homeostasis in osteoclast has not yet been identified. Transient receptor potential vanilloid (TRPV) 4, mediates Ca^<2+>influx in the late stage of osteoclast differentiation and, thereby regulates Ca^<2+> signaling. However, the system-modifying effect of TRPV4 activity remains to be determined. To elucidate the consequences of insufficient intestinal calcium absorption on calcium and bone homeostasis, and how cellular calcium homeostasis has been regulated during bone remodeling, whether 1,25(OH)_2D or calcium homeostasis influences osteoclastogenesis should be solved as an important question