Earlier detection of bone loss may be in future

TEMPE, Ariz, USA - Are your bones getting stronger or weaker? Right now, it's hard to know. Scientists at Arizona State University and NASA 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.

"Osteoporosis, a disease in which bones grow weaker, threatens more than half of Americans over age 50," explained 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.

"Bone loss also occurs in a number of cancers in their advanced stages. By the time these changes can be detected by X-rays, as a loss of bone density, significant damage has already occurred," Anbar said. "Also, X-rays aren't risk-free. We think there might be a better way."

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 published in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS) the week of May 28. It is titled "Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes."

"The paper suggests an exciting new approach to the problem," said Dr. Rafael Fonseca, chair of the Department of Medicine at the Mayo Clinic in Arizona, and a specialist in the bone-destroying disease multiple myeloma. Fonseca was not associated with the study but is partnering with the ASU team on collaborative research based on the findings.

"Right now, pain is usually the first indication that cancer is affecting bones. If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care," Fonseca said.

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," explained 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."

Other factors, especially bone destruction, also come into play, making the human body more complicated than the jelly bean analogy. But 15 years ago, corresponding author Joseph Skulan, now an adjunct professor at ASU, combined all the factors into a mathematical model that predicted that calcium isotope ratios in blood and urine should be extremely sensitive to bone mineral balance.
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