Bone loss may be detectable earlier

Scientists from NASA and Arizona State University (ASU) in the US have developed a new way of detecting bone loss that promises to be safer and capable of earlier diagnosis than current methods that rely on X-rays. They write about their work in a study due to be published in PNAS this week. Osteoporosis, where loss of bone causes bones to grow weaker, threatens more than half of the over-50s in the US. Bone loss also occurs in the advanced stages of some types of cancer. Senior author Ariel Anbar is a professor in ASU's Department of Chemistry and Biochemistry and the School of Earth and Space Exploration. He told the press: "By the time these changes can be detected by X-rays, as a loss of bone density, significant damage has already occurred." "Also, X-rays aren't risk-free. We think there might be a better way," he added. NASA is interested in this type of research because astronauts in microgravity also experience bone loss. The new method that Anbar and colleagues have developed relies on detecting tiny changes in calcium isotopes that are naturally present in urine. Patients do not need to ingest artificial tracers and are not exposed to radiation, so there is virtually no risk, say the researchers. The new technique relies on the fact that different isotopes of calcium react at slightly different rates. When bones form, the lighter isotopes enter new bone a little faster than the heavier ones, a difference called "isotope fractionation". Bone is not "dead", inert material but living tissue that is continuously undergoing formation and destruction. In healthy, active humans, these processes are in balance, but a disease can upset this balance, causing a shift in the isotope ratios. Corresponding author Joseph Skulan, an adjunct professor at ASU, combined all the factors that influence this balance into a mathematical model that predicted calcium isotope ratios in blood and urine should be very sensitive to bone mineral balance. The predicted effect is so small it has to be measured using sensitive mass spectrometry methods specially developed at ASU. For the NASA-funded study, the researchers tested urine samples of a dozen healthy volunteers who were confined to "bed rest" for 30 days. When a person lies down for a prolonged period, their weight-bearing bones, such as those in the legs and spine, experience "skeletal unloading" as a result of their loss of burden. During skeletal unloading, bones start to deteriorate as the balance between bone generation and bone destruction tips more toward destruction. Extended periods of bed rest result in bone loss similar to that seen in patients with osteoporosis and astronauts. When they analyzed the urine samples, the researchers found the new technique could spot the early signs of bone loss after just one week of bed rest, long before changes in bone density can be detected using the conventional method of dual-energy X-ray absorptiometry (DEXA). Another important feature of the new technique is that it is the only method, apart from DEXA, that measures net bone loss directly. First author Jennifer Morgan, whose doctoral work at ASU focused on developing the mass spectrometry method, said: "What we really want to know is whether the amount of bone in the body is increasing or decreasing." The team is now working on a way to evaluate the technique in samples from cancer patients. Anbar said their study is a "proof of concept", and their paper in PNAS shows "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," he added. The researchers note that the technique can be applied to many other diseases that cause subtle changes in isotope balance or in the concentration of elements. These kinds of signatures have not yet been explored in a systematic way as potential biosignatures for detecting cancers and other diseases, they said. The "concept of inorganic signatures" promises to bring in an "entirely new generation of diagnostics for cancer and other diseases", says Anna Barker, former deputy director of the National Cancer Institute, who is now director of Transformative Healthcare Networks and co-director of the Complex Adaptive Systems Initiative in the Office of Knowledge Enterprise Development at ASU.