Using natural, stable calcium isotopes of human blood to detect and monitor changes in bone mineral balance.

We are exploring variations in the Ca isotope composition of blood and urine as a new tool for early diagnosis and monitoring of changes in bone mineral balance for patients suffering from metabolic bone disease, cancers that originate in or metastasize to bone, and for astronauts who spend time in low gravity environments. Blood samples are often collected instead of, or in addition to, urine in clinical settings, so it is useful to know if variations in the Ca isotope composition of blood carry the same information as variations in urine. We found that the Ca isotope composition of blood shifts in the same direction and to the same magnitude (~2 parts per ten thousand--pptt) as that of urine in response to skeletal unloading during bed rest.

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes.

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB.

High-precision measurement of variations in calcium isotope ratios in urine by multiple collector inductively coupled plasma mass spectrometry.

We describe a new chemical separation method to isolate Ca from other matrix elements in biological samples, developed with the long-term goal of making high-precision measurement of natural stable Ca isotope variations a clinically applicable tool to assess bone mineral balance. A new two-column procedure utilizing HBr achieves the purity required to accurately and precisely measure two Ca isotope ratios ((44)Ca/(42)Ca and (44)Ca/(43)Ca) on a Neptune multiple collector inductively coupled plasma mass spectrometer (MC-ICPMS) in urine. Purification requirements for Sr, Ti, and K (Ca/Sr > 10 000; Ca/Ti > 10 000 000; and Ca/K > 10) were determined by addition of these elements to Ca standards of known isotopic composition.