UAMS Researchers Find Clue in High Rate of Broken Bones in Down Syndrome

By Jon Parham

Working with UAMS bone researchers, McKelvey focused on differences in the normal process of bone production and removal.

Larry Suva, Ph.D., director of the UAMS Center for Orthopaedic Research and professor in the Department of Orthopaedic Surgery of the UAMS College of Medicine, said that in Down syndrome, the process appears to slow down: the body is not making new bone fast enough or getting rid of older, more fragile bone rapidly enough. With osteoporosis, he said, in many cases the bone loss is occurring too fast, leading to bone weakness.

“This is a perfect example of translational research,” McKelvey said. “We see something in the clinic and then take it to our colleagues in basic science. We can then establish proof of principle, a model design that can be used to develop new treatments for our patients.”

The researchers published two recent studies on the topic. “Low bone turnover and low bone density in a cohort of adults with Down syndrome” in Osteoporosis International ( focused on the clinical observations.
“Low Bone Turnover and Low Bone Mass Density in Down Syndrome: Effect of Intermittent PTH Treatment” utilized a mouse model as a guide to intervention and new bone treatment strategies. That study was published in PLoS One and can be found at (The link to the article is:

Their work was aided by the UAMS Translational Research Institute, which provided clinical coordinator services, biostatistics help, and DEXA scans, which measure bone density.

McKelvey, an associate professor of Genetics and Family Medicine in the UAMS College of Medicine and the inaugural recipient of the Winthrop P. Rockefeller Chair in Clinical Genetics, noted that Down syndrome patients are living longer and the bone health of adolescent and adult patients has become a medical, social and economic issue. Previous researchers reported that children with Down syndrome had lower bone mass but no one studied bone turnover markers or established a potential treatment model.

“Looking at the literature, there are a range of potential factors given to explain the low bone mass, from lack of exercise and weight problems to inadequate nutrition, but there was no consistent risk factor for the patients I treated,” said McKelvey, who sees adolescents and adults with Down syndrome in the UAMS genetics clinic that opened in 2009 as a first in Arkansas and the region.

Most of the older research on those with Down syndrome compared them to mentally disabled populations and those less active, Suva said. “It was not an appropriate comparison.”

“As life expectancy of adults with Down syndrome continues to increase, it makes more sense to compare their bone physiology with adults who do not have Down syndrome,” said Suva, who is the inaugural recipient of the Carl L. Nelson Endowed Chair in Orthopaedic Creativity.

In a comparison of mouse models, the researchers found a difference in the cellular process of bone turnover – the lifelong process where older bone is removed from the skeleton and replaced with new bone. Previously researchers believed the causes of Down syndrome bone weakness was similar to the disease osteoporosis in older adults, where age and the body’s inability to stop bone deteriorating faster than it could be replaced weakened the skeleton.

“In Down syndrome, it appears the bone remodeling process is slowed down – new bone is not being made fast enough and the process slows down even more with age,” Suva said.

This knowledge could open the door to using preventative methods or treatments for increasing bone mass at an earlier age in Down syndrome patients, McKelvey said.
There are medications on the market now that can be considered, and new medications are in the pipeline to improve bone production that could have impact for the general population as well.

“This really changes our approach. The typical medicines were not working and this data explains why,” McKelvey said.

Parathyroid hormone (PTH) therapy, used to increase bone formation in osteoporosis patients, and increases bone mass Down syndrome mice but has not been approved for treating younger patients, Suva said. Another potential path is through nutritional interventions that have been shown to improve bone production.

For more information on the UAMS Down syndrome clinic please visit

UAMS colleagues joining McKelvey and Suva in the research include lead author Tristan W. Fowler, a graduate assistant in the Department of Physiology & Biophysics and Department of Orthopaedic Surgery; Nisreen S. Akel, a research assistant in the Department of Physiology & Biophysics and Department of Orthopaedic Surgery; medical student Jaclyn Vander Schilden; John W. Bracey, M.D., resident physician in Department of Orthopaedic Surgery; medical student Timothy Sowder; Robert A. Skinner, Frances L. Swain and William R. Hogue of the Department of Orthopaedic Surgery; Donna B. Leblanc, A.P.N., Department of Genetics; Dana Gaddy, Ph.D., a professor in the Department of Physiology and Biophysics; and Galen R. Wenger, Ph.D., a professor in the Department of Pharmacology and Toxicology.

UAMS is the state’s only comprehensive academic health center, with colleges of Medicine, Nursing, Pharmacy, Health Professions and Public Health; a graduate school; a hospital; a statewide network of regional centers; and seven institutes: the Winthrop P. Rockefeller Cancer Institute, the Jackson T. Stephens Spine & Neurosciences Institute, the Myeloma Institute for Research and Therapy, the Harvey & Bernice Jones Eye Institute, the Psychiatric Research Institute, the Donald W. Reynolds Institute on Aging and the Translational Research Institute. Named best Little Rock metropolitan area hospital by U.S. News & World Report, it is the only adult Level 1 trauma center in the state. UAMS has more than 2,800 students and 775 medical residents. It is the state’s largest public employer with more than 10,000 employees, including about 1,000 physicians and other professionals who provide care to patients at UAMS, Arkansas Children’s Hospital, the VA Medical Center and UAMS’ Area Health Education Centers throughout the state. Visit or