Credit: Graham Colm
Scientists have found that a technique used in Earth science research may be able to help physicians predict the course of multiple myeloma (MM).
The team showed they could use calcium isotope analysis to predict whether MM patients are at risk for developing bone lesions.
The group believes this technique could be used to chart the progression or recurrence of MM and help tailor therapies to better protect patients’ bones.
“At present, there is no good way to track changes in bone balance, except retrospectively using X-ray methods,” said Ariel Anbar, PhD, of Arizona State University in Tempe. “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 Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care.”
To explore this possibility, Drs Fonseca, Anbar, and their colleagues performed calcium isotope analysis using blood samples from MM patients. The team recounted their results in a letter to Leukemia.
As the name suggests, calcium isotope analysis measures calcium isotopes that are naturally present in blood. 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.
An earlier study testing this technique in healthy subjects 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 forming at about the same rate as it resorbs. But if bone loss is occurring, 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 using precise mass spectrometry methods.
Using these methods, the researchers tested peripheral blood samples from 71 adult patients—55 with MM, 9 with smoldering MM, and 7 with monoclonal gammopathy of undetermined significance.
The researchers found an association between how active a patient’s disease was and the change in the isotope ratios. In fact, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.
Blood samples from patients with active disease had significantly lower mean calcium isotope compositions than samples from patients with non-active disease (mean δ44/42Ca=-0.8 vs -0.67, P=0.025), regardless of diagnosis.
For MM patients specifically, those with active disease had a significantly lower mean δ44/42Ca than patients with non-active disease (-0.79 vs -0.63, P=0.016), which was consistent with resorption of bone containing lighter 42Ca.
Dr Anbar noted that, although calcium isotope analysis has worked in this small set of patients, additional research is needed to verify these initial findings and improve the efficiency of analysis.
“If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible,” he said, “and also provide the possibility to monitor the effectiveness of drugs to combat bone loss.”
