Characterization of trabecular bone structures requires necropsy of animals followed by a labor-intense histomorphometric or ex vivo micro-CT analysis. We tested the novel vivaCT40 from Scanco Medical AG (Bassersdorf, Switzerland), which allows monitoring such changes repeatedly in anesthetized rats and mice. Postmenopausal osteoporosis: in 8-month-old ovariectomized (OVX) rats, the vivaCT40 was capable of picking up the decrease in trabecular bone volume and trabecular thinning as well as the decrease in the number of trabecular elements as a function of time. The bone anabolic effects of parathyroid hormone [hPTH(1-34)], which resulted in an increase in trabecular thickness but not their number, as well as the bone protective effect of the two antiresorptive agents zoledronic acid (ZA) and 17-alpha ethinylestradiol (aEE), were detected correctly with the vivaCT40. Adjuvans arthritis: the vivaCT40 allowed measuring trabecular bone loss caused by periarticular inflammation in a rat model of adjuvans arthritis and demonstrated the bone protective effect of dexamethasone (DM). In addition, it was possible to image the subtle erosive lesions in subchondral bone caused by the inflammatory processes. Tumor osteolysis: the vivaCT40 allowed monitoring of the progressive osteolytic response following the local administration of 4T1luc2000 tumor cells into the tibia metaphysis of nude mice. The potent protective effect of ZA on tumor osteolysis was demonstrated. In summary, the new vivaCT40 can monitor the effects of known agents and diseases such as osteoporosis, inflammatory arthritis, and tumor invasion on 3-D trabecular microarchitecture accurately, repeatedly, reliably, and quickly in anesthetized rats and mice. The scanner represents a breakthrough for noninvasive imaging and structural measurements in small rodents.