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. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible.osteopenia | biomarker | medical geology | biosignature | spaceflight

Despite the importance of Fe-organic complexes in the environment, few studies have investigated Fe isotope effects driven by changes in Fe coordination that involve organic ligands. Previous experimental (Dideriksen et al., 2008, Earth Planet Sci. Lett. 269:280-290) and theoretical (Domagal-Goldman et al., 2009, Geochim. Cosmochim. Acta 73:1-12) studies disagreed on the sense of fractionation between Fe-desferrioxamine B (Fe-DFOB) and Fe(H(2)O)(6)(3+). Using a new experimental technique that employs a dialysis membrane to separate equilibrated Fe-ligand pools, we measured the equilibrium isotope fractionations between Fe-DFOB and (1) Fe bound to ethylenediaminetetraacetic acid (EDTA) and (2) Fe bound to oxalate. We observed no significant isotope fractionation between Fe-DFOB and Fe-EDTA (Delta(56/54)Fe(Fe-DFOB/Fe-EDTA) approximately 0.02 +/- 0.11 per thousand) and a small but significant fractionation between Fe-DFOB and Fe-oxalate (Delta(56/54)Fe(Fe-DFOB/Fe-Ox(3)) = 0.20 +/- 0.11 per thousand). Taken together, our results and those of Dideriksen et al. (2008) reveal a strong positive correlation between measured fractionation factors and the Fe-binding affinity of the ligands. This correlation supports the experimental results of Dideriksen et al. (2008). Further, it provides a simple empirical tool that may be used to predict fractionation factors for Fe-ligand complexes not yet studied experimentally.

Bone loss, a key concern for long-duration space travelers, is typically considered a female issue. The number of women who have flown long-duration space missions is now great enough to allow a quantitative comparison of changes in bone and renal stone risk by sex. Participants were 42 astronauts (33 men and 9 women) on long-duration missions to the International Space Station. Bone mineral density (by dual-energy X-ray absorptiometry) and biochemical markers of bone metabolism (from blood and urine samples) were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. Missions were 49 to 215 days in duration, flown between 2000 and 2012. The bone density response to spaceflight was the same for men and women in both exercise groups. The bone mineral density response to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an advanced resistive exercise device. Biochemical markers of bone formation and resorption responded similarly in male and female astronauts. The response of urinary supersaturation risk to spaceflight was not significantly different between men and women, although risks were typically increased after flight in both groups, and risks were greater in men than in women before and after flight. The responses of men and women to spaceflight with respect to these measures of bone health were not different.