HR: 0800h
AN: V51A-0517    [Abstracts]
TI: Natural variations in calcium isotope composition as a monitor of bone mineral balance in humans.
AU: Skulan, J
EM: jlskulan@geology.wisc.edu
AF: University of Wisconsin, Dept. of Geology and Geophysics, 1215 West Dayton St., Madison, WI 53701 United States
AU: Anbar, A
EM: anbar@asu.edu
AF: Dept. of Geological Sciences and Dept. of Chemistry & Biochemistry, Arizona State University, Tempe, AZ 85287 United States
AU: Thomas, B
EM: tdbullen@usgs.gov
AF: Branch of Regional Research, Water Resources Division, U.S. Geological Survey, MS 420, 345 Middlefield Rd., Menlo Park, CA 94025
AU: * Smith, S
EM: scott.m.smith@nasa.gov
AF: Human Adaptation and Countermeasures Office, Mail Code SK3, NASA Johnson Space Center, Houston, TX 77058 United States
AB: The skeleton is the largest reservoir of calcium in the human body and is responsible for the short term control of blood levels of this element. Accurate measurement of changes in bone calcium balance is critical to understanding how calcium metabolism responds to physiological and environmental changes and, more specifically, to diagnosing and evaluating the effectiveness of treatments for osteoporosis and other serious calcium-related disorders. It is very difficult to measure bone calcium balance using current techniques, however, because these techniques rely either on separate estimates of bone resorption and formation that are not quantitatively comparable, or on complex and expensive studies of calcium kinetics using administered isotopic tracers. This difficulty is even more apparent and more severe for measurements of short-term changes in bone calcium balance that do not produce detectable changes in bone mineral density. Calcium isotopes may provide a novel means of addressing this problem. The foundation of this isotope application is the ca. 1.3 per mil fractionation of calcium during bone formation, favoring light calcium in the bone. This fractionation results in a steady-state isotopic offset between calcium in bone and calcium in soft tissues, blood and urine. Perturbations to this steady state due to changes in the net formation or resorption of bone should be reflected in changes in the isotopic composition of soft tissues and fluids. Here we present evidence that easily detectable shifts in the natural calcium isotope composition of human urine rapidly reflect changes in bone calcium balance. Urine from subjects in a 17-week bed rest study was analyzed for calcium isotopic composition. Bed rest promotes net resorption of bone, shifting calcium from bone to soft tissues, blood and urine. The calcium isotope composition of patients in this study shifted toward lighter values during bed rest, consistent with net resorption of isotopically-light bone calcium. In contrast, little shift was seen in patients who exercised during bed rest, consistent with the expectation that exercise should inhibit bone resorption. Most intriguingly, an opposite-sense shift was seen in patients who were administered aledronate, a drug which inhibits bone resorption. We hypothesize that these patients entered a state of positive bone mineral balance despite initiation of bed rest. Comparison of isotopic data with measurements of bone mineral density and metabolic markers of bone metabolism confirms that the calcium isotope composition of urine reflects changes in bone mineral balance. Calcium isotope analysis of urine and soft tissues may provide information on bone mineral balance that is in important respects better than that available from other techniques, and illustrates the usefulness of applying geochemical techniques to biomedical problems.
DE: 1040 Isotopic composition/chemistry
DE: 1045 Low-temperature geochemistry
DE: 1294 Instruments and techniques
DE: 0400 Biogeosciences
SC: Volcanology, Geochemistry, Petrology [V]
MN: 2004 AGU Fall Meeting