Bone and Joint Health in Type 1 Diabetes
Scientist Shannon Wallet explores the wrecking crew that rips out the body’s old bone
Shannon Wallet, PhD
Immunologist, University of Florida College of Dentistry
Type 1 Diabetes
ADA Research Funding
Career Development Award
Bones seem like the one feature of our bodies that doesn’t move or change. But unlikely as it may seem, the 206 bones in your body are actually a lifelong work in progress: Every seven years, give or take, you get a new skeleton.
The work is done by two types of specialized cells, called osteoclasts and osteoblasts. “Osteoclasts are responsible for removing bone, and osteoblasts are responsible for laying new bone down,” says Shannon Wallet, PhD, an immunologist at the University of Florida’s College of Dentistry. “They work together to remodel the skeleton.”
To picture how it works, imagine renovating a house. There’s a demolition crew, the osteoclasts, that comes in, rips out the old, and takes it away. Only then can the osteoblasts arrive to install the new stuff. That’s just what it’s like with your bones. “To get good-quality bone, you have to remove bad-quality bone. If you don’t, over time quality and strength would be very poor,” Wallet says.
Wallet wants to know why diabetes makes the osteoclast wrecking crew go wild. In people with diabetes, “osteoclasts [break down] much more bone,” she says. “They’re overactive, and in addition they don’t turn themselves off.”
Other studies have shown that diabetes can get in the building crew’s way, too. “Osteoblasts in type 1 diabetes aren’t very good at laying down quality bone,” Wallet says. In other words, “osteoblasts don’t work well enough, and osteoclasts work too well. That’s why you end up with fragile bones.” Indeed, bone fragility and osteoporosis, a disease that reduces bone density, are both much higher in people with diabetes. It can also be harder for them to heal after breaking a bone.
Arthritis, inflammation of the joints, is another major problem. More than half of people with diabetes will have arthritis in their lifetime. The two diseases make for a particularly bad combination. According to the Centers for Disease Control and Prevention, “adults with both arthritis and diabetes were 30 percent more likely to be physically inactive than those with diabetes only, even after adjustment for age, sex, and body mass index.” It’s a vicious cycle: Arthritis makes it painful to exercise; lack of exercise makes it hard to get blood sugar under control; high blood glucose makes inflammation and arthritis worse.
People with type 1, in particular, seem to have a higher likelihood of developing arthritis, although researchers aren’t sure why. Wallet says osteoclasts and osteoblasts are responsible for bone remodeling that occurs in the joints. “It is not just breakdown of cartilage that causes arthritis, but also the bone,” she adds.
Wallet, with the help of a grant from the American Diabetes Association, is investigating the responses of osteoclasts to different anti-osteoporosis drugs. To do so, Wallet uses mice with the equivalent of type 1 diabetes to test how osteoclasts behave in a type 1 environment. It’s an important first step: There are anti-osteoporosis drugs on the market that help treat bone loss, but researchers don’t know if they also work well in people with diabetes.
By using mice, Wallet and her team can test different approaches, narrowing down which might work best before moving on to a trial in humans. “We can see if the drugs on the market are effective under these conditions,” she says. “Once we figure out the signaling process, we can augment that.”
Specifically, Wallet is trying to understand what it is about type 1 diabetes that confuses the cells responsible for removing bone. “We’re investigating the mechanism of how this works,” she says. “By evaluating the signaling process, we can understand how it’s dysfunctional in type 1 diabetes.”
Human cells, taken from donors with type 1 diabetes, can also be used in a laboratory environment. Wallet can create bone-removing osteoclasts from white blood cells, put them under different types of conditions, and see how well they respond to the body’s signals to stop once they’ve removed poor-quality bone. “If we can inhibit osteoclast activation, maybe we can improve fracture healing,” Wallet says. Ideally, the osteoclasts will then somehow signal bone-producing osteoblasts to come in and fix the bone they’ve removed.
If her research yields positive results, the next step would be to put together a drug trial in humans. In a decade—or more—treatments could be available to people with diabetes. In the meantime, Wallet’s advice is familiar. High blood sugar can lead to inflammation, which worsens the pain and progression of arthritis and osteoporosis. “This is just another really good reason to stay under glycemic control,” she says.
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