When biomedical student Seth Donahue ran into a black bear while hiking in California’s Sierra Nevada Mountains, he felt inspired rather than frightened. He wondered how the Ursus americanus, which hibernates for up to seven months a year, can wake with bones that are just as strong as they were when it first settled down for a snooze. Taking a long nap might sound like a great plan, but if a human were to do the same for only two weeks, its bones would begin to wear down from disuse.
Throughout our lifetimes, our bones are constantly being rebuilt. Over time, we lose more bone than we replace. As a result, many elderly people suffer from osteoporosis, the significant bone loss that can increase the risk of fracture. This disease affects more than 10 million Americans and is the underlying cause behind 1.5 million fractures every year (Jennings et al., 2011). Rather than develop osteoporosis, these black bears’ bodies have made evolutionary adjustments to prevent bone loss during disuse.
But how?
Tapping into the reason behind this bone restoring mechanism could offer new treatments for osteoporosis. That’s exactly what Seth Donahue, a biomedical engineer at Michigan Technological University, hypothesized.
For over a decade, Donahue and a team of research scientists have been investigating the secret behind the integrity of bears’ bones (Jennings et al., 2011). They have discovered that in bears, the trabecular, or spongy, bone that forms tissue does not lose density or volume. Working with bears was tricky, however. In an interview with the Wall Street Journal, Donahue said that bears are “not like rats where you can get 100 animals and bring them into the lab…” (Oransky et al., 2008). Donahue relied on colleagues at Virginia Tech and Washington State University to obtain samples from anesthetized hibernating bears.
These samples showed that black bears have a uniquely strong form of parathyroid hormone (PTH), which regulates the levels of blood calcium (Donahue et al., 2006). In both humans and bears, PTH is 84 amino acids long. When Donahue’s team sequenced the gene for PTH, they found nine differences in the amino acid sequence (Jennings et al., 2011). They believe that the bears evolved their distinct amino acid sequence to protect against the debilitating effects of bone disuse during hibernation. Additionally, bears maintain a constant level of PTH in their bodies throughout their dormancy, increasing the hormone’s beneficial effect.
Continuing to investigate hormonal effects on black bear bones during hibernation, the lab measured PTH in bear blood, cloned the gene for bear PTH, and used synthetic and recombinant PTH to reverse bone loss in rodent models of osteoporosis (Jennings et al., 2011). Notably, mice that received bear PTH injections over a period of weeks developed stronger bones. This suggests that a treatment of bear PTH could also help humans with diseases, like osteoporosis, that involve bone atrophy.
What are the next steps for getting black bear PTH available to patients suffering from osteoporosis? A 5-year-old Kalamazoo-based biotechnology company, Aursos Inc., has been developing a drug based upon Donahue’s technology. The company plans to target the smaller market of people suffering from Duchenne’s muscular dystrophy (DMD) before making its product, bear PTH1-84, available to the millions of people with osteoporosis. DMD is an inherited neuromuscular disease that has harmful consequences for muscle and bone, causing osteoporosis. Clinical trials on patients with this rare disease may show the efficacy of the bear PTH1-84 treatment.
If black bear PTH passes the test of DMD treatment, it could compete with currently available osteoporosis drugs. These include biphosphonates and calcitonin, which can reduce bone loss and fracture risk (Kerriem-Norwood et al., 2011). A synthetic PTH drug, Forteo, builds new bone, but comes with black box warnings for cancer risks.
If the bear PTH treatment with its unique amino acid sequence is more effective in humans than Forteo, a smaller and less dangerous dose can be delivered. The scientific study of black bears could aid patients who suffer from age, disease, or disuse-related osteoporosis.
As Ursus americanus hunkers down this fall, it can only dream of the possibilities it has created for new DMD and osteoporosis treatments.
In Brief:
- Researchers from Michigan Technological University are learning how black bears can hibernate without waking up with brittle bones.
- They have identified parathyroid hormone as a potential reason for the bears’ strong bones.
- This research could lead to improved osteoporosis treatments.
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