Development of new treatments for metabolic bone disease, and evaluation of the effectiveness of existing therapies in individual patients, are severely hampered by the lack of any reliable tool for quickly measuring changes in bone mineral balance in response to treatment. A new tracerless calcium isotope biomarker of bone mineral balance fills this need. When properly applied, the calcium isotope biomarker reveals changes in bone mineral balance with unprecedented speed and detail, and has the potential to dramatically improve the treatment for diseases such as osteoporosis. A complementary strontium isotope biomarker provides, with equal rapidity, information on the speed of exchange of calcium between soft tissue and mineralized compartments.

Two related inventions are described here along with novel chemical purification and mass spectrometric techniques developed to facilitate the isotopic measurements underlying the inventions. Both inventions involve the use of elements from natural sources with natural isotope compositions (as opposed to tracers artificially enriched with one or more isotopes) as biomarkers to measure magnechanges in bone mineral balance. The first is a tracer-less calcium isotope technique that measures net bone mineral balance by analyzing changes in the natural isotope composition of calcium in blood and urine resulting from the balance of bone formation vs. resorption. This is the only known technique to measure net bone mineral balance before the onset of bone loss. The second is a strontium isotope tracer technique that exploits natural variations in 87Sr/86Sr to create and sustain an isotopic offset between dietary strontium and strontium originating in bone, which can be used to measure the rate of bone mineral loss. This technique differs from standard isotope tracer techniques, which give no direct information on bone mineral loss and require administration of a radioactive isotope.

The inventions directly measure bone mineral balance, not just bone formation or resorption. The inventions measure changes in bone mineral balance with unprecedented speed, and long before these changes have had a measurable effect on bone mineral density. The inventions are the first proposed clinical applications of calcium and strontium stable isotopes, and among the only proposed clinical applications of any stable isotopes. The calcium isotope biomarker is the only technique involving calcium isotopes that does not require the administration of an artificial isotopic tracer. The strontium isotope technique is the only technique involving any element that uses naturally occurring isotopic mixtures as tracers. All other calcium isotope techniques employ artificially prepared isotopic tracers. These are fundamentally different from the techniques described here, and provide no direct information on bone mineral balance.

The inventions measure net bone mineral balance on short time scales. Markers of bone formation and resorption are commonly employed in research on metabolic bone disease, and can be used to estimate bone mineral balance. The potential utility of the inventions as research tools is not limited to their application to current investigations of bone biology. The inventions allow short-term changes in bone mineral balance to be observed for the first time, opening up large new areas of research.

This work was done by Ariel Anbar, Gwyneth Gordon, and Jennifer L. Morgan of Arizona State University; and Joseph Skulan for Johnson Space Center. For further information, contact the JSC Technology Transfer Office at (281) 483-3809. MSC-25390-1