Letters to the Editor: Serum Markers of Bone Metabolism Show Bone Loss in Hibernating Bears

Abstract

Reply: Floyd et al3 proposed that black bears (Ursus americanus) produce an osteoregulatory substance to prevent disuse osteoporosis during hibernation.3 We agree that this is a viable hypothesis. For example, bears may have a novel growth factor. We also hypothesize that the calcium regulatory hormones calcitonin and parathyroid hormone (PTH) play an important role in bone metabolism during hibernation because serum calcium levels remain constant.3 We have attempted to measure the levels of calcitonin and PTH in black bear serum, however, there are currently no cross-reacting antibodies available to determine these hormones in black bears. Given that leptin is a potent inhibitor of bone formation,2 we also hypothesize that leptin has an important bone remodeling regulatory role in black bears during disuse. However, as of yet, we have not tried to measure leptin levels in black bear serum. We are grateful for the insightful comments of Cizza et al and we now plan to quantify leptin levels in future studies. Cizza et al proposed that a decrease in leptin is the biologic factor responsible for minimizing bone loss in hibernating bears. However, steep and continuously rising leptin levels, beginning approximately 1 month before hibernation, has been reported for European brown bears.4 Recently, we studied seasonal variations in the bone formation marker PICP during a 196-day period, which included 3 months of prehibernation, 3 months of hibernation, and one posthibernation period of blood sampling (unpublished data). We found no significant differences in serum PICP levels between the prehibernation and hibernation periods, but saw a sharp increase in PICP at the posthibernation sampling. We propose that the increase in bone formation during the posthibernation period is a compensatory response to the increase in bone resorption that occurs during hibernation. Interestingly, our PICP data show an apparent negative correlation with the data of Hissa et al4 At arousal, bone formation is high and leptin levels are low, whereas at prehibernation, bone formation is low and leptin levels are high. Therefore, although the hypothesis of Cizza et al of a regulatory influence of leptin on bone remodeling is plausible, the available evidence suggests that the seasonal variations in leptin levels are opposite those proposed by Cizza et al Given the role of leptin in appetite suppression, our suggestion that leptin levels increase before and during hibernation fits better with the observation, by us and Hissa at al,4 that bears become anorectic just before hibernation and do not eat during hibernation. Cizza et al also proposed that leptin, and not a stimulatory mechanical input to bone cells minimizes bone loss during disuse. This is in contrast to our original hypothesis that bone-forming osteoblasts are sensitized to mechanical stimulation during remobilization at spring arousal, possibly by circulating hormone levels.1 We maintain that this is a viable hypothesis. Hormones, including PTH, sensitize bone cells to mechanical stimulation in vitro.5 We think that many factors, including leptin, PTH, other hormones, and possibly novel growth factors, are likely to play a coordinated role in the regulation of bone remodeling to prevent disuse osteoporosis in hibernating black bears, and that several of these mechanisms warrant additional investigation. The biologic mechanisms that regulate bone remodeling in black bears are complex phenomena and understanding this process may give rise to new therapies for osteoporosis. Seth W. Donahue, PhD Department of Biomedical Engineering, Michigan Technological University, Houghton, MI Michael R. Vaughan, PhD U.S. Geological Survey, Virginia Cooperative Fish and Wildlife Research Unit, Virginia Polytechnic Institute and State University, Blacksburg, VA Laurence M. Demers, PhD Departments of Pathology and Medicine, The Pennsylvania State University, Hershey, PA Henry J. Donahue, PhD Musculoskeletal Research Laboratory, Department of Orthopaedics and Rehabilitation, The Pennsylvania State University, Hershey, PA