ALBERT

Description: Serum calcium (Ca), bone biomarkers and radiological imaging do not allow accurate evaluation of bone mineral balance (BMB), a key determinant of bone mineral density (BMD) and fracture risk. We studied naturally occurring stable (non‐radioactive) Ca isotopes in different body pools as a potential biomarker of BMB. 42Ca and 44Ca are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation; isotopically light 42Ca is preferentially incorporated into bone, whereas heavier 44Ca preferentially remains in blood and is excreted in urine and feces. Their ratio (δ44/42Ca) in serum and urine increases during bone formation and decreases with bone resorption. In 117 healthy participants we measured Ca isotopes, biomarkers, and BMD by DXA and tibial peripheral quantitative CT (pQCT). 44Ca and 42Ca were measured by multi‐collector ionization‐coupled plasma mass‐spectrometry in serum, urine and feces. The relationship between bone Ca gain and loss was calculated using a compartment model. δ44/42Caserum and δ44/42Caurine were higher in children (n=66, median age 13 years) compared to adults (n=51, median age 28 years; p〈0.0001 and p=0.008 respectively). δ44/42Caserum increased with height in boys (p〈0.001, R2=0.65) and was greatest at Tanner stage 4. δ44/42Caserum correlated positively with biomarkers of bone formation (25‐hydroxyvitaminD [p〈0.0001, R2=0.37] and alkaline phosphatase [p=0.009, R2=0.18]) and negatively with bone resorption marker PTH (p=0.03, R2=0.13). δ44/42Caserum strongly positively correlated with tibial cortical BMD‐Z‐score (n=62; p〈0.001, R2=0.39), but not DXA. Independent predictors of tibial cortical BMD‐Z‐score were δ44/42Caserum (p=0.004, β=0.37), 25‐hydroxyvitaminD (p=0.04, β=0.19) and PTH (p=0.03, β=‐0.13), together predicting 76% of variability. In conclusion, naturally occurring Ca isotope ratios in different body compartments may provide a novel, non‐invasive method of assessing bone mineralization. Defining an accurate biomarker of BMB could form the basis of future studies investigating Ca dynamics in disease states and the impact of treatments that affect bone homeostasis.