In most animals, physical inactivity leads to altered bone remodeling and loss of bone mineral, structural, and mechanical properties. Complete recovery of this lost bone typically requires a remobilization period that is 2-3 times longer than the disuse period. Bears, however, experience annual periods of disuse (hibernation) and recovery that are approximately equal in length, yet they maintain cortical bone tissue level material properties with age. The mechanism by which bears maintain bone mass despite experiencing annual disuse periods may be linked to calcium recycling, and therefore may be governed by the effects of bear parathyroid hormone (PTH). Bear PTH levels are positively correlated with a serum marker of bone formation in hibernating bears, and interestingly, synthetic bear PTH 1-34 promotes osteoblast survival better than synthetic human PTH 1-34 (a current treatment for osteoporosis) in vitro. Thus, bear PTHH may have potential to be translated into a new therapy for osteoporosis.

It is unclear from previous studies 1) if bears preserve whole bone mechanical and structural properties with age, 2) if cortical bone properties are different in bears before and after hibernation (i.e., if bears can completely prevent cortical bone loss during hibernation), 3) how hibernation affects cortical bone remodeling in bears, 4) whether bears are unique among hibernating animals in their ability to prevent disuse-induced cortical bone loss, and 5) whether bear PTH is an effective osteogenic agent in vivo, and if its anabolic effects are comparable or superior to human PTH, the only anabolic treatment for osteoporosis that is currently commercially available. To address these issues, we measured whole bone strength, bone geometrical properties, cortical bone microstructural properties (e.g., porosity), and histological indices of intracortical bone remodeling in bears before, during, and after hibernation. We also investigated similar properties in hibernating and active 13-lined ground squirrels, and compared the in vivo anabolic effects of synthetic bear PTH 1-34 to human PTH 1-34 in an animal model. Results from these studies support the idea that bears possess a unique biological mechanism to prevent disuse osteoporosis. Further research to elucidate this mechanism may eventually contribute to the development of new therapies to treat human osteoporosis.