Texas A&M researchers uncover new insights into bone healing challenges for people with Down syndrome

Around 350,000 people in the United States have Down syndrome (DS), a genetic condition associated with lower bone mass and increased risk of bone fracture. Research from Texas A&M University has previously shown that when people with DS get bone fractures, they often do not heal, which can be fatal.

Now, thanks to a $1.8 million grant from the National Institutes of Health, researchers from the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) have discovered that bone healing also gets worse as people with DS grow older.

“Down syndrome is associated with both decreased bone degradation and bone formation, which are the two main stages of bone healing,” said Dr. Lindsay Dawson, an assistant professor in the VMBS’ Department of Veterinary Physiology and Pharmacology (VTPP). The Dawson lab is a regeneration biology lab that strives to understand what controls poor regeneration outcomes in animals, with the ultimate goal of regenerating human limbs and enhancing quality of life after traumatic injury.

“Bone degradation is similar to cleaning up a building site before laying the foundation of a new structure. Bone formation is when the bone actually starts to repair itself,” she said.

Thanks to advances in medicine, people with DS are living longer, more active lives, but this can put them at greater risk for developing bone injuries.

“In our recently published study, we wanted to understand how bone health changes across the lifespan in people with DS,” Dawson said. “Using a model of DS, one of our findings was that bone healing is much worse for males as they age. We also found that it’s possible for females to develop poor outcomes to bone healing after they reach middle age, even if they previously had no issues when younger.”

While DS is also associated with accelerated aging, Dawson and her team were able to show that issues with bone healing may have a separate cause.

“People with DS often have early onset menopause, thyroid dysfunction, early onset Alzheimer’s disease and cartilage and bone abnormalities associated with aging,” said Sarah Wolff, a VTPP doctoral student. “Our data shows that poor bone healing is not simply a result of accelerated aging.”

Ultimately, Dawson, Wolff and the rest of the research team hope to use the discoveries funded by their grant to develop treatments, reducing the threat of bone fracture and increasing quality of life for people with DS.

Any regenerative treatments that Dawson and her colleagues develop will also be useful for helping people with limb loss.

“Around 2.1 million people in the U.S. are living with limb loss, and that number is expected to more than triple by the year 2060 because of the increase in vascular diseases like diabetes,” Dawson said. “Understanding how bone regeneration works is key to developing new treatments, including the possibility of regrowing entire limbs.”

Finding solutions to complex problems

To develop a treatment that can help mend bone injuries in people with DS, scientists must first understand how and why these injuries are so stubborn.

“One of the interesting things we discovered in these recent studies is that other bodily systems — like the ability to heal a skin wound — are unaffected here,” Dawson said. “The problems that are present are very specific to bone healing.

“This is good news because, once we find all of the bone healing genes that are affected by DS, we’ll be able to narrow things down and develop a regenerative medicine strategy,” she said.

Though Dawson and her team have already uncovered key information useful for developing a treatment for poor bone healing in DS, they’re continuing to approach their target from new angles.

“One of our ongoing studies will use a different model that lets us account for the variability of humans,” she said. “No two people are the same, even if they both have DS. We want to develop a treatment that will help real people, and that means understanding how individuals are different.”

Dawson and her team are also conducting a study that will focus on older middle age health, using a model that can represent people with DS up to 50 years old.

In addition, they plan to start testing possible treatments, including different anabolic agents that are known for promoting bone growth.