Calcium isotope analysis predicts myeloma progression

A team of researchers is showing how a staple of Earth science research can be used in biomedical settings to predict the course of disease. The researchers used calcium isotope analysis to predict whether myeloma patients are at risk for developing bone lesions, a hallmark of the disease.

They believe they have a promising technique that could be used to chart the progression of multiple myeloma, a lethal disease that eventually impacts a patient's bones. The method could help tailor therapies to protect bone better and also monitor for possible disease progression or recurrence. The research, carried out by Arizona State University (ASU) and Mayo Clinic in Tempe, Arizona, was published in Leukemia (2014; doi:10.1038/leu.2014.193).

"Multiple myeloma is a blood cancer that can cause painful and debilitating bone lesions," said co-lead author Gwyneth Gordon, PhD, an associate research scientist at ASU's School of Earth and Space Exploration. "We wanted to see if we could use isotope ratio analysis, a common technique in geochemistry, to detect the onset of disease progression."

The researchers explained that changes in bone balance cannot currently be tracked, except through retrospective x-rays. Then, the data comes after the damage has occurred.

"Right now, pain is usually the first indication that cancer is affecting the bones," added Rafael Fonseca, MD, Chair of the Department of Medicine at the Mayo Clinic. "If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care."

The technique measures the naturally occurring calcium isotopes that the researchers believe can serve as an accurate near-real-time detector of bone metabolism for multiple myeloma patients. Bone destruction in myeloma manifests itself in bone lesions, osteoporosis, and fractures.

With the method, bone loss is detected by carefully analyzing the isotopes of calcium that are naturally present in blood. 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 for the test. The only harm done with the new method is a pinprick for a blood draw.

The technique makes use of a fact well known to Earth scientists but not normally used in biomedicine, which is that different isotopes of a chemical element can react at slightly different rates. An earlier study showed that 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 to the method.

In healthy, active humans bone is in balance, meaning bone is forming at about the same rate as it dissolves (resorbs). But if bone loss is occurring, then the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.

With the new test, the ASU-Mayo Clinic researchers found that there was an association between how active the disease was and the change in the isotope ratios. In addition, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.

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