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J Bone Miner Res, 2020; (): , PMID: 32786145

Naturally occurring stable calcium isotope ratios in body compartments provide a novel biomarker of bone mineral balance in children and young adults.

Year: 2020

Shroff R, Fewtrell M, Heuser A, Kolevica A, Lalayiannis A, McAlister L, Silva S, Goodman N, Schmitt CP, Biassoni L, Rahn A, Fischer DC, Eisenhauer A
Renal Unit, UCL Great Ormond Street Hospital for Children NHS Foundation Trust, Institute of Child Health, London, UK.


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. (42) Ca and (44) Ca are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation; isotopically light (42) Ca is preferentially incorporated into bone, whereas heavier (44) Ca preferentially remains in blood and is excreted in urine and feces. Their ratio (delta(44/42) Ca) 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). (44) Ca and (42) Ca 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. delta(44/42) Caserum and delta(44/42) Caurine 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). delta(44/42) Caserum increased with height in boys (p<0.001, R(2) =0.65) and was greatest at Tanner stage 4. delta(44/42) Caserum correlated positively with biomarkers of bone formation (25-hydroxyvitaminD [p<0.0001, R(2) =0.37] and alkaline phosphatase [p=0.009, R(2) =0.18]) and negatively with bone resorption marker PTH (p=0.03, R(2) =0.13). delta(44/42) Caserum strongly positively correlated with tibial cortical BMD-Z-score (n=62; p<0.001, R(2) =0.39), but not DXA. Independent predictors of tibial cortical BMD-Z-score were delta(44/42) Caserum (p=0.004, beta=0.37), 25-hydroxyvitaminD (p=0.04, beta=0.19) and PTH (p=0.03, beta=-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.

GID: 5181; Last update: 25.08.2020