(KATV, Source: UAMS) Little Rock - UAMS geneticist and Down
syndrome expert Kent McKelvey, M.D., knew there had to be something more to the
high rate of broken bones in those with the genetic condition than just typical
osteoporosis.
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 (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 to
intervention and new bone treatment strategies. That study was published in PLoS
One and can be found by clicking here. More specifically, for the article, click here.
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, click here.
