Decreased mechanical use of the skeleton results in osteoporosis in all species that have been studied, including humans. The unique metabolic adaptations of denning bears, however, suggest that these animals have evolved osteoregulatory mechanisms to protect against osteoporosis. The authors studied calcium and bone metabolism in black bears during three seasons: summer, winter, and spring. The serum calcium concentration did not change despite the fact that the bears remained metabolically active, recumbent, and anuric for four months. Furthermore, after four months of skeletal inactivity, bone mass and other parameters of osseous metabolism, including bone formation and mineral apposition rates were unchanged over summer values. A hypermetabolic state was observed after spring arousal in response to resumed skeletal loading. These findings suggest that bears may produce an osteoregulatory mechanism that prevents bone loss during prolonged periods of skeletal inactivity. Such a substance could have potential therapeutic applications for human beings.