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"Osteoporosis, a disease in which bones grow weaker, threatensmore than half of Americans over age 50," explained ArielAnbar, a professor in ASU's Department of Chemistry andBiochemistry and the School of Earth and Space Exploration, andsenior author of the study. "Bone loss also occurs in a number of cancers in theiradvanced stages. By the time these changes can be detected byX-rays, as a loss of bone density, significant damage has alreadyoccurred," Anbar said. "Also, X-rays aren't risk-free. Wethink there might be a better way." With the new technique, bone loss is detected by carefullyanalyzing the isotopes of the chemical element calcium that arenaturally present in urine. Isotopes are atoms of an element thatdiffer in their masses. Patients do not need to ingest anyartificial tracers and are not exposed to any radiation, so thereis virtually no risk, the authors noted. The findings are presented in a paper published in the online EarlyEdition of the Proceedings of the National Academy of Sciences ( PNAS ) the week of May 28. It is titled "Rapidly assessing changesin bone mineral balance using natural stable calciumisotopes." "The paper suggests an exciting new approach to theproblem," said Dr. Rafael Fonseca, chair of the Department ofMedicine at the Mayo Clinic in Arizona, and a specialist in thebone-destroying disease multiple myeloma. Fonseca was notassociated with the study but is partnering with the ASU team oncollaborative research based on the findings. "Right now, pain is usually the first indication that canceris affecting bones. If we could detect it earlier by an analysis ofurine or blood in high-risk patients, it could significantlyimprove their care," Fonseca said. The new technique makes use of a fact well known to Earthscientists, but seldom used in biomedicine: Different isotopes of achemical element can react at slightly different rates. When bonesform, the lighter isotopes of calcium enter bone a little fasterthan the heavier isotopes. That difference, called "isotopefractionation," is the key. "Instead of isotopes of calcium, think about jellybeans," explained Jennifer Morgan, lead author of the study."We all have our favorite. Imagine a huge pile of jelly beanswith equal amounts of six different kinds. You get to make your ownpersonal pile, picking out the ones you want. Maybe you pick twoblack ones for every one of another color because you really likelicorice. It's easy to see that your pile will wind up with moreblack jelly beans than any other color. Therefore, the ratio ofblack to red or black to green will be higher in your pile than inthe big one. That's similar to what happens with calcium isotopeswhen bones form. Bone favors lighter calcium isotopes and picksthem 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 anadjunct professor at ASU, combined all the factors into amathematical model that predicted that calcium isotope ratios inblood and urine should be extremely sensitive to bone mineralbalance. "Bone is continuously being formed and destroyed," Skulanexplained. "In healthy, active humans, these processes are inbalance. But if a disease throws the balance off then you ought tosee a shift in the calcium isotope ratios." The predicted effect on calcium isotopes is very small, but can bemeasured using sensitive mass spectrometry methods developed byMorgan as part of her doctoral work with Anbar, Skulan andco-author Gwyneth Gordon, an associate research scientist in theW.M. Keck Foundation Laboratory for Environmental Biogeochemistryat ASU. Co-author Stephen Romaniello, currently a doctoral studentwith Anbar at ASU, contributed an updated mathematical model. The new study, funded by NASA, examined calcium isotopes in theurine of a dozen healthy subjects confined to bed ("bedrest") for 30 days at the University of Texas Medical Branchat Galveston's Institute for Translational Sciences-ClinicalResearch Center. Whenever a person lies down, the weight-bearingbones of the body, such as those in the spine and leg, are relievedof their burden, a condition known as "skeletalunloading." With skeletal unloading, bones start todeteriorate due to increased destruction. Extended periods of bedrest induce bone loss similar to that experienced by osteoporosispatients, and astronauts. "NASA conducts these studies because astronauts inmicrogravity experience skeletal unloading and suffer boneloss," said co-author Scott M. Smith, NASA nutritionist."It's one of the major problems in human spaceflight, and weneed to find better ways to monitor and counteract it. But themethods used to detect the effects of skeletal unloading inastronauts are also relevant to general medicine." Lab analysis of the subjects' urine samples at ASU revealed thatthe new technique can detect bone loss after as little as one weekof bed rest, long before changes in bone density are detectable bythe conventional approach, dual-energy X-ray absorptiometry (DEXA). Importantly, it is the only method, other than DEXA, that directlymeasures net bone loss. "What we really want to know is whether the amount of bone inthe body is increasing or decreasing," said Morgan. Calcium isotope measurements seem poised to assume an importantrole in detecting bone disease -- in space, and on Earth. The teamis working now to evaluate the technique in samples from cancerpatients. "This is a 'proof-of-concept' paper," explained Anbar"We showed that the concept works as expected in healthypeople in a well-defined experiment. The next step is to see if itworks as expected in patients with bone-altering diseases. Thatwould open the door to clinical applications." However, the concept extends even beyond bone and calcium, theauthors noted. Many diseases may cause subtle changes in elementisotope abundances, or in the concentrations of elements. Thesesorts of signatures have not been systematically explored in thedevelopment of biosignatures of cancers and other diseases. "The concept of inorganic signatures represents a new andexciting approach to diagnosing, treating and monitoring complexdiseases such as cancer," stated Anna Barker, director ofTransformative Healthcare Networks and co-director of the ComplexAdaptive Systems Initiative in the Office of Knowledge EnterpriseDevelopment at ASU. Barker, who came to ASU after being deputydirector of the National Cancer Institute, emphasized thesimplicity of the approach compared to the challenges ofdeciphering complex genome-derived data, adding "there is anopportunity to create an entirely new generation of diagnostics forcancer and other diseases.". I am an expert from outdoor-ledfloodlight.com, while we provides the quality product, such as E27 Light Fitting , E40 LED Light, Indoor LED Flood Lights,and more.
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