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Goldschmidt2015 – the world’s pre-eminent geochemistry conference

Geochemists developing ‘near real-time’ osteoporosis and bone cancer test with aid of NASA astronauts

Embargo until: 00.05 Central European Summer Time (Prague), Tuesday 18 th August, 2015

A new test for offers the possibility of near real time monitoring of bone diseases, such as osteoporosis and multiple myeloma. The functionality of the test, which measures changes in calcium isotope ratios, has been validated on blood samples from NASA space shuttle astronauts.

Our bones are largely built of calcium, and the turnover of calcium can indicate the development of bone diseases such as osteoporosis and the cancer multiple myeloma. Geochemists have developed extremely accurate ways of measuring calcium isotope ratios, for example for the study of sea shell deposits in sedimentary rocks. Now a group of US geochemists, biologists and clinicians, from

Arizona State University and the Mayo Clinic, have worked with NASA to put these techniques together to develop a new, rapid test of bone health.

These methods, using mass spectrometry, can discern the relative ratios of the calcium isotopes 42 Ca and 44 Ca in bone. The researchers found that lighter calcium isotopes, such as 42 Ca, are absorbed from the blood into the bone during bone formation. Conversely, these light isotopes tend to be released into the bloodstream when bones break down. By measuring the ratios of the two isotopes in blood or urine scientists can calculate the rate of change of bone mass

According to lead researcher, Ariel Anbar(Arizona State University):

“The big advantage of these measurements is that they show what is happening in the bone, whereas traditional bone health measurements, such as DXA scans, show what has happened. This means that we can have a real near-time view of what is happening in the bone, rather than comparing before and after, when damage may have already been done”.

“Our goal is that these measurements will allow us to see bone breakdown in osteoporosis, but also can show us the progress of certain bone cancers, such as multiple myeloma”.

The research was piloted in bed-bound subjects (who lose bone mass), but the best way for the researchers to test whether the system worked was in an ambient and less controlled population who are known to experience rapid bone loss. In space, because of zero gravity conditions, astronauts experience very rapid bone loss. Working with NASA, the researchers measured calcium isotope ratios in urine from 30 shuttle astronauts, before, during, and after the flights. This allowed them to confirm that the test worked at high sensitivity (NASA partly funded the research).

Ariel Anbar said:

“We were able to confirm that Ca isotopes of the shuttle shifted as expected, meaning that they we could see in more or less real time the ongoing bone loss. We did this using a simple urine sample, taken at various points during their flights”.

The researchers have also looked at a group of 71 patients who either had multiple myeloma (bone cancer), or were at risk of multiple myeloma.

“What we saw with cancer patients was interesting. Those patients who tended to lose the lighter

42 Ca isotope seemed to be the ones where the cancer was the most active. This means that the tests could theoretically feed into decisions on whether or not to treat a patient, for example if a cancer was dormant or growing very slowly, and to assess the effectiveness of treatments”.

He continued

“At the moment, this is still a test which is in development, but we have shown it can work. There is work to be done to further validate the tests, and costs to consider, however the advantage for this methodology is that the patient doesn’t have to come to the machine; the measurements can be done with a blood or urine test. And from a scientific point of view, we are delighted that we have the chance to combine geochemistry, biology, and space science to benefit patients”.

Commenting, Scott Parazynski, MD, former NASA astronaut, currently University Explorer and

Professor at Arizona State University said:

“It’s tremendous to see a sophisticated geochemical assay being translated into what could become a really significant medical diagnostic tool. Physicians treating osteoporosis and other calcium disorders of bone, including multiple myeloma, have very few tools at their disposal to quickly determine whether the treatments they’re providing are actually making a difference. By using calcium isotope ratios, healthcare providers may be able to optimize therapies for these debilitating illnesses in the future.”

ENDS

Notes for Editors

Please mention the Goldschmidt conference in any story resulting from this press release

Contact details

Dr Ariel Anbar anbar@asu.edu

Goldschmidt Press Officer, Tom Parkhill: tom@parkhill.it

tel +39 349 238 8191

The Goldschmidt Conference is the world’s most important geochemistry conference. Around 3000 delegates will attend the 25 th Anniversary 2015 Goldschmidt conference in Prague ( http://goldschmidt.info/2015/ ), from

16-21 August. The Goldschmidt Conference is co-sponsored by the Geochemical Society and the European

Association of Geochemistry . Goldschmidt2016 takes place in Yokohama, Japan.

Background

 54million Americans (mostly women) suffer from osteoporosis or low bone density, http://nof.org/news/2948

There are around 27,000 new cases of multiple myeloma in the US every year, http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics

ABSTRACT

Developing a clinically useful calcium isotope biomarker ARIEL D. ANBAR1,2*, GWYNETH W. GORDON 1, JOSEPH L.

SKULAN3, SCOTT M. SMITH4, RAFAEL FONSECA5 1 School of Earth and Space Exploration, Arizona State University, Tempe,

AZ 85287, USA (*correspondence: anbar@asu.edu

) 2Department of Chemistry & Biochemistry, Arizona State University,

Tempe, AZ 85287, USA 3 Elemental Biomarkers, LLC, 7820 Caribou Ct, Vernon, WI 53593, USA 4Human Health Performance

Directorate, NASA Johnson Space Center, Houston, TX 77058, USA 5Mayo Clinic, Scottsdale, AZ 85259, USA

Near-real-time monitoring of bone metabolism in metabolic bone diseases such as osteoporosis and multiple myeloma

(MM) would help clinicians detect disease onset earlier than is currently possible. A biomarker detecting asymptomatic bone destruction would also help evaluate the efficacy of bone-specific therapies. We are developing naturally occurring

Ca isotope ratios ( 44/42Ca) in serum and urine as such a biomarker. We previously reported that natural changes in

44/42Ca of urine provide quantitative information on short-term changes in net bone mineral balance, information unavailable from conventional biochemical measures of bone metabolism. The basis of this biomarker is that blood and urine are enriched or depleted in light Ca isotopes as a consequence of net bone gain or loss, respectively. In our studies of bed-rest induced bone loss, a net bone mineral loss rate of about <4%/year is detectable, consistent with results of X-Ray densitometry. Here, we report data in clinically relevant populations. Bed-rest induces bone loss due to unloading, and so is used to model the effects of space flight on bone metabolism. Hence, we examined Ca isotopes in urine samples from 30 astronauts on International Space Station missions. We find a systematic shift toward preferential excretion of lighter Ca isotopes during flight, correlated with increased Ca excretion. The results are consistent with expectations from bed-rest.

Extending into populations with active bone disease, we examined Ca isotopes in serum collected from 71 adult patients diagnosed with either MM or asymptomatic precursor diseases. Samples of patients with active disease had statistically significant lower mean 44/42Ca than those with non-active disease, regardless of diagnosis. The significant relationship between 44/42Ca and myeloma activity is likely due to a myeloma-induced increased level of bone resorption.

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