Hibernating black bears shed light on treatments for osteoporosis

Unlike humans, bears seem to recover from bone loss caused by inactivity

Wild black bears may hold some secrets to preserving bone in humans.

Researchers at Penn State Milton S. Hershey Medical Center and Michigan Technological University recently studied the animal’s unique ability to rebound from significant bone loss suffered each year during hibernation. Their study, published in the March 2003 issue of Clinical Orthopedics and Related Research, shows that wild black bears have a built-in coping mechanism that ensures that yearly hibernation doesn’t leave the bears’ bones too fragile.

“In humans, disuse or immobilization as a result of bed rest or injury causes rapid bone loss, which may not be completely recoverable and can lead to weakness and fractures,” said Henry J. Donahue, Ph.D., professor of orthopedics and rehabilitation, Musculoskeletal Research Laboratory, Penn State Milton S. Hershey Medical Center. “With this study, our goal was to determine how bears recover from five to seven months of hibernation each year, which can cause them significant bone loss due to disuse.”

Seth Donahue, Ph.D., a former post-doctoral fellow at Penn State College of Medicine, and an assistant professor of biomedical engineering, Michigan Technological University, added, “the black bear’s mechanism of bone recovery may even provide insight into other, more common bone diseases like age-related osteoporosis and provide a rationale for the development of new pharmacological therapies.” In addition to the aging and those confined to bed, bone loss is also a problem for those with spinal cord injuries and astronauts exposed to microgravity during extended space flight.

In the study, blood samples were obtained from radio-collared wild black bears during winter denning and active summer periods. Blood samples were collected at Virginia Polytechnic Institute and State University following procedures approved by the Virginia Tech Animal Care Committee. A total of 17 bears were a part of the study: seven males ages one to seven years; six females ages one to 12 years with cubs; and four females ages one to 17 years without cubs. Bears went into hibernation in December and came out in mid-April. For the sample collected during hibernation, researchers confirmed that bears had denned from one to three months.

After collection, the blood was spun in a centrifuge to attain the blood serum, the liquid portion of the blood free of red cells and clotting agents. Then, radioimmunoassays were performed to determine serum concentrations of three substances: cortisol; the carboxy-terminal cross-linked telopeptide (ICTP) – a marker of bone loss; and the carboxy-terminal propeptide of type I procollagen (PICP) – a marker of bone formation.

Higher concentrations of ICTP or PICP in the serum indicate that a bear is losing bone or forming bone, respectively. Although its role is somewhat unclear, cortisol, a naturally-occurring steroid hormone, has been shown to have a negative effect on bone density in humans. The same serum markers of bone loss and formation measured in this study already have proven useful for assessing bone status in humans with osteoporosis.

In the study of bears, results showed that ICTP and serum cortisol significantly increased during hibernation for all bears. However, PICP was not significantly different during the denning period than in the active period. Females who gave birth in the den showed relative increases in bone loss and larger decreases in bone formation than other bear groups, but the differences were not significant when compared with the other bear groups. PICP, the bone formation marker, was four- to fivefold higher in an adolescent and 17-year-old bear early in the active period compared with later in the summer months.

The data suggests that bears, like other animals, lose bone during extended periods of disuse. However, humans and other animals tend also to decrease bone formation during sedentary periods.

“These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining the same level of bone formation as when they’re active,” Seth Donahue said. Because bears do not urinate or defecate during hibernation, it is likely that the calcium freed in the body due to bone loss is reused in bone formation.

With the yearly hibernation period roughly equal to the active period, and with bone formation taking longer than bone loss, how do bears maintain bone long term?

“They may be able to make more rapid and complete recoveries during remobilization than other animals,” Seth Donahue said. “The bone formation marker was four- to fivefold higher in early remobilization months in two female bears.

One possible mechanism for complete recovery is that bone cells in bears are more sensitive to mechanical stimulation and circulating hormone levels during remobilization and therefore rebuild bone faster.” Because the researchers were limited as to when they could collect samples, it’s unclear whether all the bears experienced elevated bone formation in the period immediately following hibernation.

“These findings lend support to the hypothesis that black bears have the ability to minimize bone loss during disuse by maintaining bone formation and completely recover lost bone by increasing bone formation during remobilization,” Henry J. Donahue said.

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This work was supported by a National Institute of Aging, National Institutes of Health, grant (R01-AG13087) awarded to Henry J. Donahue, Ph.D. Other research team members were: Michael Vaughan, Ph.D., U.S. Geological Survey, Virginia Cooperative Fish and Wildlife Research Unit, Virginia Polytechnic Institute and State University; and Laurence M. Demers, Ph.D., Departments of Pathology and Medicine, Penn State College of Medicine, Penn State Hershey Medical Center.