Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis

Eisenhauer, Anton; Müller, Marius; Heuser, Alexander; Kolevica, Ana; Glüer, Claus‐C.; Both, Marieke I; Laue, Christiane; Hehn, Ulrike von; Kloth, Stefan; Shroff, Rukshana; Schrezenmeir, J.

doi:10.1016/j.bonr.2019.100200

Cited by 54 publications

(72 citation statements)

References 22 publications

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“…Approximately 250 μL serum, 1000 μL urine, and 100 mg feces were used for analysis. Full details of the Ca isotope measurements have been previously described (19) and are summarized in the Supplemental Materials and Methods. Supplemental Table S1.…”

Section: Ca Isotope Measurementsmentioning

confidence: 99%

“…(15) Isotopically light Ca is preferentially enriched during chemical transport reactions (for example, incorporation into bone), whereas the heavy isotope is preferentially excreted in urine and feces. (16,(18)(19)(20)(21) The ratio of Ca isotopes (for example, when studying 42 Ca and 44 Ca, the ratio would be expressed as δ 44/42 Ca) gives a direct function of the state of bone turnover. Thus, when bone formation exceeds bone resorption and the net BMB is positive, the δ 44/42 Ca serum isotope values are higher compared with δ 44/42 Ca serum values measured under conditions when bone resorption is the predominant process.…”

Section: Introductionmentioning

confidence: 99%

“…Ca isotope ratios in urine and feces reflect serum isotope values and are similarly high during bone formation and low during bone resorption. (16,22) The relationship between Ca isotope fractions in serum and urine is described mathematically in a compartment model (16,18,19,21,23) that in turn is used to quantitatively determine net bone gain or loss of Ca.…”

Section: Introductionmentioning

confidence: 99%

“…(18) In a study in older women, those with osteoporosis confirmed by dual-energy X-ray absorptiometry (DXA) scan had significantly lower δ 44/42 Ca serum and δ 44/42 Ca Urine values compared with agematched controls without osteoporosis. (19) The sensitivity of natural Ca isotope fractionation measures has been further studied in animal models (14,17,24) and healthy adults, (16,20,22,23,(25)(26)(27)(28) where δ 44/42 Ca in serum and urine closely reflected the interventions to alter bone homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults

Shroff

Fewtrell

Heuser

et al. 2020

Journal of Bone and Mineral Research

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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 (δ 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 dual-energy X-ray absorptiometry (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. δ 44/42 Ca serum and δ 44/42 Ca urine were higher in children (n = 66, median age 13 years) compared with adults (n = 51, median age 28 years; p < 0.0001 and p = 0.008, respectively). δ 44/42 Ca serum increased with height in boys (p < 0.001, R 2 = 0.65) and was greatest at Tanner stage 4. δ 44/42 Ca serum 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 parathyroid hormone (PTH; p = 0.03, R 2 = 0.13). δ 44/42 Ca serum 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 δ 44/42 Ca serum (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.

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Section: Ca Isotope Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults

Shroff

Fewtrell

Heuser

et al. 2020

Journal of Bone and Mineral Research

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“…The amount of calcium in blood is determined by a calcium blood test [65]. Nearly all (99%) of calcium is stored in bone, and the remaining 1% is found in blood.…”

Section: Calcium Blood Testmentioning

confidence: 99%

Advances in Sensing Technologies for Monitoring of Bone Health

et al. 2020

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Changing lifestyle and food habits are responsible for health problems, especially those related to bone in an aging population. Poor bone health has now become a serious matter of concern for many of us. In order to avoid serious consequences, the early prediction of symptoms and diagnosis of bone diseases have become the need of the hour. From this inspiration, the evolution of different bone health monitoring techniques and measurement methods practiced by researchers and healthcare companies has been discussed. This paper focuses on various types of bone diseases along with the modeling and remodeling phenomena of bones. The evolution of various diagnosis tests for bone health monitoring has been also discussed. Various types of bone turnover markers, their assessment techniques, and recent developments for the monitoring of biochemical markers to diagnose the bone conditions are highlighted. Then, the paper focuses on the potential assessment of the recent sensing techniques (physical sensors and biosensors) that are currently available for bone health monitoring. Considering the importance of electrochemical biosensors in terms of high sensitivity and reliability, specific attention has been given to the recent development of electrochemical biosensors and significance in real-time monitoring of bone health.

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High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool

Vanhaecke

Costas‐Rodríguez

2020

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All elements with two or more isotopes show natural variation in their isotopic composition as a result of the isotope fractionation that accompanies (bio)chemical reactions and (bio)physical processes. Multicollector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) offers the precision required to reveal and quantify the differences in isotope ratios thus caused, although they are often of sub‐permil magnitude only. Using MC‐ICP‐MS, it has been shown that (a) in different body compartments, essential mineral elements may display different isotopic compositions, and (b) disease conditions may alter the isotopic composition of an essential mineral element in a biofluid and/or tissue. As a result, high‐precision isotopic analysis of these elements is a powerful way to unravel the actual role these essential mineral elements play in specific biochemical processes. Moreover, isotope ratio shifts also show promise as a diagnostic or prognostic tool. Despite the intensive sample pretreatment preceding MC‐ICP‐MS isotopic analysis and the high purchase and running costs of the instrumentation, this approach may be valuable, especially for diseases that can otherwise only be established at a later stage and/or via a more invasive approach. This review paper describes the basics of “biomedical isotopic analysis” and uses selected cases from the literature to sketch the state‐of‐art and illustrate in which context isotope ratio markers could be exploited in a clinical context.

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Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis

Cited by 54 publications

References 22 publications

Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults

Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults

Advances in Sensing Technologies for Monitoring of Bone Health

High‐precision isotopic analysis of essential mineral elements: capabilities as a diagnostic/prognostic tool

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