Working with UAMS bone researchers, McKelvey focused ondifferences in the normal process of bone production and removal.
Larry Suva, Ph.D., director of the UAMS Center for OrthopaedicResearch and professor in the Department of Orthopaedic Surgery of the UAMSCollege of Medicine, said that in Down syndrome, the process appears to slowdo the body is not making new bone fast enough or getting rid of older, morefragile bone rapidly enough. With osteoporosis, he said, in many cases the boneloss 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 ourcolleagues in basic science. We can then establish proof of principle, a modeldesign 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 Downsyndrome" in Osteoporosis International (http://www.ncbi.nlm.nih.gov/pubmed/22903293)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 tointervention and new bone treatment strategies. That study was published in PLoSOne and can be found by clicking here. More specifically, for the article, click here.
McKelvey, an associateprofessor of Genetics and Family Medicine in the UAMS College of Medicine andthe inaugural recipient of the Winthrop P. Rockefeller Chair in ClinicalGenetics, noted that Down syndrome patients are living longer and the bonehealth of adolescent and adult patients has become a medical, social andeconomic issue. Previous researchers reported that children with Down syndromehad lower bone mass but no one studied bone turnover markers or established apotential treatment model.
"Looking at the literature, there are a range of potentialfactors given to explain the low bone mass, from lack of exercise and weightproblems to inadequate nutrition, but there was no consistent risk factor forthe patients I treated," said McKelvey, who sees adolescents and adults withDown syndrome in the UAMS genetics clinic that opened in 2009 as a first inArkansas and the region.
Most of the older research on those with Down syndromecompared them to mentally disabled populations and those less active, Suvasaid. "It was not an appropriate comparison."
"As life expectancy of adults with Down syndrome continuesto increase, it makes more sense to compare their bone physiology with adultswho do not have Down syndrome," said Suva, who is the inaugural recipient of the Carl L. Nelson Endowed Chair inOrthopaedic Creativity.
In a comparison of mouse models, the researchers found adifference in the cellular process of bone turnover - the lifelong processwhere older bone is removed from the skeleton and replaced with new bone.Previously researchers believed the causes of Down syndrome bone weakness wassimilar to the disease osteoporosis in older adults, where age and the body'sinability to stop bone deteriorating faster than it could be replaced weakenedthe skeleton.
"In Down syndrome, it appears the bone remodeling process isslowed down - new bone is not being made fast enough and the process slows downeven more with age," Suva said.
This knowledge could open the door to using preventativemethods or treatments for increasing bone mass at an earlier age in Downsyndrome patients, McKelvey said.
There are medications on the market now that can beconsidered, and new medications are in the pipeline to improve bone productionthat could have impact for the general population as well.
"This really changes our approach. The typical medicineswere not working and this data explains why," McKelvey said.
Parathyroidhormone (PTH) therapy, used to increase boneformation in osteoporosis patients, and increases bone mass Down syndrome mice buthas not been approved for treating younger patients, Suva said. Anotherpotential path is through nutritional interventions that have been shown toimprove bone production.
For more information on the UAMS Down syndrome clinic, click here.