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Earlier Detection of Bone Loss May Be Possible in the Future
06.20.12
 
iss030e012663 -- Dan Burbank exercises using the advanced Resistive Exercise Device

NASA astronaut Dan Burbank, Expedition 30 commander, exercises using the advanced Resistive Exercise Device (aRED) in the Tranquility node of the International Space Station. Space station crew members use the aRED and other exercise devices to help maintain bone density. Credit: NASA

Are your bones getting stronger or weaker? Right now, it's hard to know. Scientists at NASA and Arizona State University are taking on this medical challenge by developing and applying a technique that originated in the Earth sciences.

In a new study, this technique was more sensitive in detecting bone loss than the X-ray method used today, with less risk to patients. Eventually, it may find use in clinical settings, and could pave the way for additional innovative biosignatures to detect disease.

"NASA conducts these studies because astronauts in microgravity experience skeletal unloading and suffer bone loss," said co-author Scott M. Smith, NASA nutritionist at the Johnson Space Center. "It's one of the major problems in human spaceflight, and we need to find better ways to monitor and counteract it. But the methods used to detect the effects of skeletal unloading in astronauts are also relevant to general medicine."

"Osteoporosis, a disease in which bones grow weaker, threatens more than half of Americans over age 50,” said Ariel Anbar, a professor in ASU's Department of Chemistry and Biochemistry and the School of Earth and Space Exploration, and senior author of the study.

With the new technique, bone loss is detected by carefully analyzing the isotopes of the chemical element calcium that are naturally present in urine. Isotopes are atoms of an element that differ in their masses. Patients do not need to ingest any artificial tracers and are not exposed to any radiation, so there is virtually no risk, the authors noted.

The findings are presented in a paper recently published in the Proceedings of the National Academy of Sciences (PNAS). It is titled "Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes."

The new technique makes use of a fact well known to Earth scientists, but seldom used in biomedicine: Different isotopes of a chemical element can react at slightly different rates. When bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called "isotope fractionation," is the key.

"Instead of isotopes of calcium, think about jelly beans," said Jennifer Morgan, lead author of the study. "We all have our favorite. Imagine a huge pile of jelly beans with equal amounts of six different kinds. You get to make your own personal pile, picking out the ones you want. Maybe you pick two black ones for every one of another color because you really like licorice. It's easy to see that your pile will wind up with more black jelly beans than any other color. Therefore, the ratio of black to red or black to green will be higher in your pile than in the big one. That's similar to what happens with calcium isotopes when bones form. Bone favors lighter calcium isotopes and picks them over the heavier ones."

The new study, funded by NASA, examined calcium isotopes in the urine of a dozen healthy subjects confined to bed ("bed rest") for 30 days at the University of Texas Medical Branch at Galveston's Institute for Translational Sciences–Clinical Research Center. Whenever a person lies down, the weight-bearing bones of the body, such as those in the spine and leg, are relieved of their burden, a condition known as "skeletal unloading.”

With skeletal unloading, bones start to deteriorate due to increased destruction. Extended periods of bed rest induce bone loss similar to that experienced by osteoporosis patients and astronauts on long-duration missions.

Lab analysis of the subjects' urine samples at ASU revealed that the new technique can detect bone loss after as little as one week of bed rest, long before changes in bone density are detectable by the conventional approach, dual-energy X-ray absorptiometry (DEXA).

Importantly, it is the only method, other than DEXA, that directly measures net bone loss.

"What we really want to know is whether the amount of bone in the body is increasing or decreasing", said Morgan.

Calcium isotope measurements seem poised to assume an important role in detecting bone disease – in space, and on Earth. The team is working now to evaluate the technique in samples from cancer patients.

"This is a 'proof-of-concept' paper," said Anbar "We showed that the concept works as expected in healthy people in a well-defined experiment. The next step is to see if it works as expected in patients with bone-altering diseases. That would open the door to clinical applications."

However, the concept extends even beyond bone and calcium, the authors noted. Many diseases may cause subtle changes in element isotope abundances, or in the concentrations of elements. These sorts of signatures have not been systematically explored in the development of biosignatures of cancers and other diseases.

To view the ASU press release, visit:

https://asunews.asu.edu/now_headlines

The PNAS paper is available for free download at:

http://www.pnas.org/content/early/2012/05/30/1119587109.full.pdf+html