I nvestigating apparent drivers of urinary Ca isotope variability in a sample population

Isotopes of calcium (Ca) in blood and urine have been introduced as a potential clinical tool for monitoring bone mineral balance (BMB). While several works support the ability of Ca isotope composition (δ44/42Ca) to capture a shift in BMB in response to external forcings (e.g. bed rest) or disease (e.g. osteoporosis), the influence of an individual's demographic, health status, diet or lifestyle on δ44/42CaUrine/Blood remains largely unconstrained. To gauge the effects of several variables among these four broader categories, we present a population study of δ44/42CaUrine from 103 individuals (age 18-76). Age is negatively correlated with δ44/42CaUrine, and we identify three other attributes (active vitamin D deficiency, vegetarian diet, and being post-menopausal) that lead to systematic differences in an individual's δ44/42CaUrine. Fluctuations in Ca reabsorption generate significant intra-individual δ44/42CaUrine variability. Within a typical range of reabsorption rates, however, the initial isotope composition (δ44/42CaSerum) exerts the strongest control on inter-individual δ44/42CaUrine variability. Using a simple Rayleigh model to express isotopic fractionation associated with Ca reabsorption in the kidneys, we find that a fractionation factor of 0.99972 reproduces the range of isotope ratios and excretion values for several, healthy individuals across three different studies and nearly a 30-year age span. Importantly, δ44/42CaUrine variations in three post-menopausal women from three separate studies cannot be explained by the same model, pointing to a different mechanistic control of δ44/42CaUrine in these subjects.