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Interpretation of 41Ca data using compartmental modeling in post-menopausal women

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Abstract

Calcium-41 (t 1/2 = 105 years) can be used after a single dose to follow calcium metabolism over a subject's lifetime. The aims of this study were to expand a 41Ca kinetic model and estimate bone resorption in women with stable bone loss, compare the rates with those calculated with classical isotope studies, and to use the model to simulate dynamic changes in urinary 41Ca:Ca ratios and bone balance for the design and interpretation of 41Ca studies. Forty-two women >5 years post-menopause were given 41Ca intravenously. Bone mineral content and bone mineral density of total body were measured by dual-energy X-ray absorptiometry at the beginning of the study. Urine collections were made periodically for up to ∼5 years while subjects were free living. Urinary 41Ca:Ca ratios were measured using accelerator mass spectrometry. The isotope data were analyzed by compartmental modeling. Four compartments were necessary to fit the urinary tracer data and total bone calcium. The final model included pathways for absorption, distribution, urinary excretion, and endogenous excretion and was used to calculate rates of bone turnover. Estimates of bone resorption in a subset of the women (n = 13), studied previously in a 3-week balance and full kinetic study with 45Ca, agreed with those using 41Ca methodology. Thus, rates of bone resorption can be estimated from 41Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary 41Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation.

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References

  1. Looker AC, Bauer DC, Chesnut CH 3rd, Gundberg CM, Hochberg MC, Klee G, Kleerekoper M, Watts NB, Bell NH (2000) Clinical use of biochemical markers of bone remodeling: current status and future directions. Osteoporos Int 11(6):467–480

    Article  CAS  Google Scholar 

  2. Leeming DJ, Alexandersen P, Karsdal MA, Qvist P, Schaller S, Tanko LB (2006) An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice. Eur J Clin Pharmacol 62(10):781–792

    Article  CAS  Google Scholar 

  3. Hui SL, Zhou L, Evans R, Slemenda CW, Peacock M, Weaver CM, McClintock C, Johnston CC Jr (1999) Rates of growth and loss of bone mineral in the spine and femoral neck in white females. Osteoporos Int 9(3):200–205

    Article  CAS  Google Scholar 

  4. Jackson GS, Weaver C, Elmore D (2001) Use of accelerator mass spectrometry for studies in nutrition. Nutr Res Rev 14(2):317–334

    Article  CAS  Google Scholar 

  5. Denk E, Hillegonds D, Vogel J, Synal A, Geppert C, Wendt K, Fattinger K, Hennessy C, Berglund M, Hurrell RF, Walczyk T (2006) Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism. Anal Bioanal Chem 386(6):1587–1602

    Article  CAS  Google Scholar 

  6. Denk E, Hillegonds D, Hurrell RF, Vogel J, Fattinger K, Hauselmann HJ, Kraenzlin M, Walczyk T (2007) Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass. J Bone Miner Res 22(10):1518–1525

    Article  CAS  Google Scholar 

  7. Recker R, Lappe J, Davies K, Heaney R (2000) Characterization of perimenopausal bone loss: a prospective study. J Bone Miner Res 15(10):1965–1973

    Article  CAS  Google Scholar 

  8. Cheong JMK, Martin BR, Jackson GS, Elmore D, McCabe GP, Nolan JR, Barnes S, Peacock M, Weaver CM (2007) Soy isoflavones do not affect bone resorption in postmenopausal women: a dose-response study using a novel approach with 41Ca. J Clin Endocrinol Metab 92(2):577–582

    Article  CAS  Google Scholar 

  9. Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M (2009) Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using 41Ca methodology. J Clin Endocrinol Metab 94(10):3798–3805

    Article  CAS  Google Scholar 

  10. Elmore D, Conard N, Kubik PW, Fabryka-Martin J (1984) Computer controlled isotope ratio measurements and data analysis. Nucl Instrum Methods Phys Res B 5(2):233–237

    Article  Google Scholar 

  11. Wastney ME, Martin BR, Peacock M, Smith D, Jiang XY, Jackman LA, Weaver CM (2000) Changes in calcium kinetics in adolescent girls induced by high calcium intake. J Clin Endocrinol Metab 85(12):4470–4475

    Article  CAS  Google Scholar 

  12. Wastney ME, Patterson BH, Linares OA, Greif PC, Boston RC (1999) Investigating biological systems using modeling: strategies and software. Academic Press, San Diego

    Google Scholar 

  13. Neer R, Berman M, Fisher L, Rosenberg LE (1967) Multicompartmental analysis of calcium kinetics in normal adult males. J Clin Invest 46(8):1364–1379

    CAS  Google Scholar 

  14. Spence LA, Lipscomb ER, Cadogan J, Martin B, Wastney ME, Peacock M, Weaver CM (2005) The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study. Am J Clin Nutr 81(4):916–922

    CAS  Google Scholar 

  15. Cooper AR, Forbes RM, Mitchell HH (1956) Further studies on the gross composition and mineral elements of the adult human body. J Biol Chem 223(2):969–975

    CAS  Google Scholar 

  16. O'Flaherty EJ (1998) A physiologically based kinetic model for lead in children and adults. Environ Health Perspect 106(Suppl 6):1495–1503

    Google Scholar 

  17. O'Flaherty EJ (2000) Modeling normal aging bone loss, with consideration of bone loss in osteoporosis. Toxicol Sci 55(1):171–188

    Article  Google Scholar 

  18. Dawson-Hughes B (1996) Calcium and vitamin D nutritional needs of elderly women. J Nutr 126(4 Suppl):1165S–1167S

    CAS  Google Scholar 

  19. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354(8):821–831

    Article  CAS  Google Scholar 

  20. Freeman SPHT, King JC, Vieira NE, Woodhouse LR, Yergey AL (1997) Human calcium metabolism including bone resorption measured with 41Ca tracer. Nucl Instrum Methods Phys Res B 123:266–270

    Article  CAS  Google Scholar 

  21. Freeman SPHT, Beck B, Bierman J, Caffee MW, Heaney RP, Holloway L, Marcus R, Southon JR, Vogel JS (2000) The study of skeletal calcium metabolism with 41Ca and 45Ca. Nucl Instrum Methods Phys Res B 172(1–4):930–933

    Article  CAS  Google Scholar 

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Acknowledgements

This study is funded by Purdue University, University of Alabama Botanical Center for Age Related Diseases, and National Institutes of Health (NIH) grants P50 AT00477.

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Authors and Affiliations

  1. Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN, 47907-2093, USA

    Wang-Hee Lee

  2. Metabolic Modeling Services Ltd, Blenheim, New Zealand

    Meryl E. Wastney

  3. PRIME Lab, Purdue University, West Lafayette, IN, 47907-2036, USA

    George S. Jackson

  4. Department of Foods and Nutrition, Purdue University, 700 West State St, West Lafayette, IN, 47907-2059, USA

    Berdine R. Martin & Connie M. Weaver

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  1. Wang-Hee Lee
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  2. Meryl E. Wastney
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  3. George S. Jackson
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  4. Berdine R. Martin
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  5. Connie M. Weaver
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Correspondence to Connie M. Weaver.

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Lee, WH., Wastney, M.E., Jackson, G.S. et al. Interpretation of 41Ca data using compartmental modeling in post-menopausal women. Anal Bioanal Chem 399, 1613–1622 (2011). https://doi.org/10.1007/s00216-010-4454-5

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  • DOI: https://doi.org/10.1007/s00216-010-4454-5

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