Using natural stable calcium isotopes to rapidly assess changes in bone mineral balance using a bed rest model to induce bone loss

Abstract

Spaceflight and metabolic bone diseases disrupt normal bone mineral balance (BMB) resulting in bone loss. Bed rest, by stimulating bone loss, provides the opportunity to evaluate new methods to monitor BMB in healthy individuals suffering bone loss. Natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes preferentially, while bone resorption releases that isotopically light Ca back into soft tissue (Skulan & DePaolo, 1999). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before measurable changes in bone mineral density (BMD) occur. The Ca isotope variations are consistent with changes observed in urinary N‐teleopeptide, a bone resorption marker. Bone specific alkaline phosphatase, a bone formation marker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate changes in the Ca isotope ratio to changes in BMD using a mathematical model. This model predicts that subjects lost 0.25 ± 0.07% (± SD) of their bone mass from day 7 to 30 of bed rest, consistent with bone loss rates from 90 day bed rest studies as measured by DXA scans. The rapid signal observed using Ca isotopes and the potential to quantitatively assess bone loss makes this technique particularly well suited for the study of bone metabolism.Grant Funding Source: NASA Human Research Program. Dr. Morgan is supported through an appointment to the NASA Postdoctoral Program at JSC, administered by ORAU.