Assessing Myeloma Progression Using Calcium Isotope Analysis

Scientists are revealing how an Earth science research principle can be used in biomedical situations to predict the development of disease.

The researchers evaluated a new approach to detecting bone loss in cancer patients by using calcium isotope analysis to predict whether myeloma patients are at risk for developing bone lesions, a key characteristic of the disease. They believe they have a potential way to chart the progression of multiple myeloma, a deadly disease that ultimately impacts a patient’s bones. The technique could help customize therapies to protect bone better and also act as a way to monitor for possible disease progression or recurrence.

“Multiple myeloma is a blood cancer that can cause painful and debilitating bone lesions,” said Dr. Gwyneth Gordon, an associate research scientist in Arizona State University’s (ASU; Tempe, USA) School of Earth and Space Exploration, and co-lead author of the study. “We wanted to see if we could use isotope ratio analysis, a common technique in geochemistry, to detect the onset of disease progression.”

“At present, there is no good way to track changes in bone balance except retrospectively using X-ray methods,” said Ariel Anbar, a professor in ASU’s School of Earth and Space Exploration and the department of chemistry and biochemistry. “By the time the X-rays show something the damage has been done.”

“Right now, pain is usually the first indication that cancer is affecting the bones,” added Dr. Rafael Fonseca, chair of the department of medicine at the Mayo Clinic (Rochester, MN, USA), and a member of the research team. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care,” he added.

The researchers, which include Drs. Gordon, Melanie Channon, and Prof. Anbar from ASU and Drs. Jorge Monge (co-lead author), Qing Wu, and Fonseca from Mayo Clinic, described the tests and their findings in an early on-line edition June 12, 2014, of the Nature publication Leukemia.

The technique measures the naturally occurring calcium isotopes that the researchers think can serve as an effective near-real-time detector of bone metabolism for multiple myeloma patients. Bone destruction in myeloma manifests itself in osteoporosis, bone lesions, and fractures. The ASU-Mayo Clinic research builds on an earlier [US] National Aeronautics and Space Administration (NASA; Houston, TX, USA) study by the ASU team. That research focused on healthy individuals participating in an experiment. “This is the first demonstration that the technique has some ability to detect bone loss in patients with disease,” said Prof. Anbar, a biogeochemist at ASU.

With the technology, bone loss is identified 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 that occurred with the new method, according to Prof. Anbar, 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—different isotopes of a chemical element can react at slightly different rates. The earlier NASA 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 technology.

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. The effect on calcium isotopes is very small, typically less than a 0.02% change in the isotope ratio. But even effects that small can be measured by using precise mass spectrometry methods available at ASU.

With the new test, the ASU-Mayo Clinic researchers found that there was a link between how active the disease was and the change in the isotope ratios. Furthermore, the isotope ratios forecasted disease activity better than, and independent from, standard clinical variables.

Prof. Anbar noted that while the technology has worked on a small group of patients, more still needs to be done to validate initial findings and enhance the effectiveness of analysis. “If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”

Related Links:
Arizona State University 
Mayo Clinic