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Calcium-41: a technology for monitoring changes in bone mineral

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Abstract

The rare, long-lived radiotracer, 41Ca, measured by accelerator mass spectrometry in the urine or serum following incorporation into the bone provides an ultra-sensitive tool to assess changes in bone calcium balance in response to an intervention. Changes in bone balance can be followed for years with one small dose that is both radiologically and biologically non-invasive. Sequential interventions can be compared, with greater precision than they can with biochemical markers of bone turnover and with greater power than with bone densitometry. This method is especially useful to screen interventions over a period of weeks. The development and validation of this tool and its applications are reviewed. Mini abstract: Use of 41Ca measured in the urine or blood by accelerator mass spectrometry to assess bone balance provides a tool to compare the relative efficacy of multiple interventions. This perspective provides insights in the use of this novel method and comparisons with more traditional methods for evaluating the efficacy of interventions.

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References

  1. Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Br Med J 12:1254–1259

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Johnson RR et al (1994) Calcium resorption from bone in a human studied by 41Ca tracing. Nucl. Inst. and Meth. in Phys. Res. B 92:483–488

    Article  CAS  Google Scholar 

  4. Freeman SPHT et al (1997) Human calcium metabolism including bone resorption measured with 41Ca tracer. Nucl Inst and Meth in Phys Res B 123:266–270

    Article  CAS  Google Scholar 

  5. Vockenhuber C et al (2015) Efficient Ca-41 measurements for biomedical applications. Nucl Instr & Meth Phys Res Section B-Beam Interactions with Materials and Atoms 361:273–276

    Article  CAS  Google Scholar 

  6. Klein M et al (2013) The 1 MV multi-element AMS system for biomedical applications at the Netherlands Organization for Applied Scientific Research (TNO). Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms 294:14–17

    Article  CAS  Google Scholar 

  7. Muller P et al (2000) Trace detection of Ca-41 in nuclear reactor concrete by diode-laser-based resonance ionization mass spectrometry. Radiochim Acta 88:487–493

    CAS  Google Scholar 

  8. Muller P et al (2001) Ca-41 ultratrace determination with isotopic selectivity >10(12) by diode-laser-based RIMS. Fresenius Journal of Anal Chem 370:508–512

    Article  CAS  Google Scholar 

  9. Wendt K, Trautmann N, Bushaw BA (2000) Resonant laser ionization mass spectrometry: an alternative to AMS? Nucl Instr & Meth in Phys Res B 172:162–169

    Article  CAS  Google Scholar 

  10. Villareal DT, Binder EF, Williams DB, Schechitman KB, Yarasheski KE, Korht WM (2001) Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial. JAMA 286:815–820

    Article  CAS  PubMed  Google Scholar 

  11. Leung JY, Ho AY, Ip TP, Lee G, Kung AW (2005) The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in osteoporotic Chinese women: a randomized placebo-controlled study. Bone 36:358–364

    Article  CAS  PubMed  Google Scholar 

  12. Harris ST, Ericksen EF, Davidson M, Ettinger MP, Moffett AH Jr, Baylink DJ, Crusan CE, Chines AA (2001) Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 86:1890–1897

    CAS  PubMed  Google Scholar 

  13. 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 to estradiol or risedronate in postmenopausal women using 41Ca methodology. J Clin Endocrinol Metab 94:3798–3805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhao Y, Cheong JMK, Lee WH, Wastney M, Martin BR, Weaver CM (2010) Tetracycline and calcium kinetics are comparable in estimating bone resorption in rats. J Nutr 140:1704–1709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cheong J, Gunaratna N, McCabe G, Jackson G, Kempa-Steczko A, Weaver C (2011) Bone seeking labels as markers for bone turnover: validation of urinary excretion in rats. Osteoporosis Intl 22:153–157

    Article  CAS  Google Scholar 

  16. Lee W-H, Wastney ME, Jackson GS, Martin BR, Weaver CM (2011) Interpretation of 41Ca data using compartmental modeling in post-menopausal women. Anal Bioanal Chem 399:1613–1622

    Article  CAS  PubMed  Google Scholar 

  17. 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 and renal handling in postmenopausal women: a randomized cross over study. Am J Clin Nutr 81:916–922

    CAS  PubMed  Google Scholar 

  18. Wastney ME, Ng J, Smith D, Martin BR, Peacock M, Weaver CM (1996) Differences in calcium kinetics between adolescent girls and young women. Am J Phys 271:R208–R216

    CAS  Google Scholar 

  19. Sharma M, Bajzer Z, Hui SK (2011) Development of 41Ca-based pharmacokinetic model for the study of bone remodeling in humans. Clin Pharmacokinet 50:191–199

    Article  CAS  PubMed  Google Scholar 

  20. Turner CH (1999) Toward a mathematical description of bone biology: the principle of cellular accommodation. Calcif Tissue Int 65:466–471

    Article  CAS  PubMed  Google Scholar 

  21. Hohman EE, McCabe GP, Peacock M, Weaver CM (2014) Validation of urinary calcium isotope excretion from bone for screening anabolic therapies for osteoporosis. Osteoporos Int 25:2471–2475

    Article  CAS  PubMed  Google Scholar 

  22. Toromanoff A, Ammann P, Mosekilde L, Thomsen JS, Riond JL (1997) Parathyroid hormone increases bone formation and improves mineral balance in vitamin D-deficient female rats. Endocrinol 138:2449–2457

    CAS  Google Scholar 

  23. Recker R, Lappe J, Davies KM, Heaney R (2004) Bone remodeling increases substantially in years after menopause and remains increased in older osteoporotic patients. J Bone Min Res 19:1628–1633

    Article  Google Scholar 

  24. Rogers TS, Garrod MG, Peerson JM, Hillegonds DJ, Buchholz BA, Demmer E, Richardson C, Gertz ER, Van Loan MD (2016) Is bone equally responsive to calcium and vitamin D intake from food vs. supplements? Use of 41Ca tracer kinetic model. Bone Reports 5:117–123

    Article  PubMed  PubMed Central  Google Scholar 

  25. Freeman SPHT, Beck B, Bierman JM, Caffee MW, Heaney RP, Holloway L, Marcus R, Southon JR, Vogel JS (2000) The study of skeletal Ca metabolism with 41Ca and 45Ca. Nucl Instr and Meth B 172:930–933

    Article  CAS  Google Scholar 

  26. Cheong JMK, Gunaratna NS, McCabe GP, Jackson JS, Weaver CM (2009) Bone seeking labels as markers for bone turnover: effect of dosing schedule on labeling various bone sites in rats. Calcif Tissue Intl 85(5):444–450

    Article  CAS  Google Scholar 

  27. Denk E, Hillegonds D, Hurrell RF, Vogel J, Fattinger K, Häuselmann 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 22:1518–1525

    Article  CAS  PubMed  Google Scholar 

  28. Freeman SPHT, Serfass RE, King JC, Southon JR, Fang Y, Woodhouse LR, Bench GS, McAninch JE (1995) Biological sample preparation and 41Ca AMS measurement at LLNL. Nucl Instr and Meth B 99:557–561

    Article  CAS  Google Scholar 

  29. Lin Y, Hillegonds DJ, Gertz ER, VanLoan MD, Vogel JS (2004) Protocol for assessing bone health in humans by tracing long-lived 41Ca isotope in urine, serum, and saliva samples. Anal Biochem 332:193–1955

    Article  CAS  PubMed  Google Scholar 

  30. Jakeman SA, Henry CN, Martin BR, McCabe GP, McCabe LD, Jackson GS, Peacock M, Weaver CM (2016) Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial. Am J Clin Nutr 104:837–843

    Article  CAS  PubMed  Google Scholar 

  31. Pawlowski J, Martin B, McCabe G, McCabe L, Jackson G, Peacock M, Barnes S, Weaver CM (2015) Impact of equol producing capacity and soy isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a partially randomized crossover trial. Am J Clin Nutr 102:695–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Alekel DL, Van Loan MD, Koehler KJ, Hanson LN, Stewart JW, Hanson KB, Kurzer MS, Peterson CT (2010) The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr 91:218–230

    Article  CAS  PubMed  Google Scholar 

  33. Tai TY, Tsai KS, Tu ST, Wu JS, Chang CI, Chen CL, Shaw NS, Peng HY, Wang SY, Wu CH (2012) The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study. Osteoporos Int 23:1571–1580

    Article  CAS  PubMed  Google Scholar 

  34. Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J (2011) Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double blind trial. Arch Inter Med 171:1363–1369

    Article  CAS  Google Scholar 

  35. Brewer L, Williams D, Moore A (2011) Current and future treatment options in osteoporosis. Eur J Clin Pharmacol 67:321–331

    Article  CAS  PubMed  Google Scholar 

  36. Pawlowski J, Martin B, McCabe G, Ferruzzi M, Weaver C (2014) Plum and soy aglycon extracts superior at increasing bone calcium retention in ovariectomized Sprague Dawley rats. J Ag Food Chem 62:6108–6114

    Article  CAS  Google Scholar 

  37. Hohman E, McCabe G, Weaver C (2011) Soy isoflavones, alone or in combination with risedronate, do not reduce bone resorption in ovariectomized rats. J Bone Min Res 26:MO0467

    Google Scholar 

  38. Fitzgerald RL, Hillegonds DJ, Burton DW, Griffin TL, Mullaney S, Vogel JS, Deftos LJ, Herold DA (2005) 41Ca and accelerator mass spectrometry to monitor calcium metabolism in end stage renal disease patients. Clin Chem 51:2095–2102

    Article  CAS  PubMed  Google Scholar 

  39. Hui SK, Prior J, Gelbart Z, Johnson RR, Lentle BC, Paul M (2007) A pilot study of the feasibility of long-term human bone balance during perimenopause using a 41Ca tracer. Nucl Instr and Meth B 259:796–800

    Article  CAS  Google Scholar 

  40. Park CY, Lee WH, Fleet JC, Allen MR, McCabe GP, Walsh DM, Weaver CM (2014) Calcium and vitamin D intake maintained from preovariectomy independently affect calcium metabolism and bone properties in Sprague Dawley rats. Osteoporos Int 25:1905–1915

    Article  CAS  PubMed  Google Scholar 

  41. Setchell KDR, Zhao X, Jha P, Heubi J, Brown N (2009) The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereroisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Am J Clin Nutr 90:1029–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Parfitt AM (2003) Misconceptions (3): calcium leaves bone only by resorption and enters only by formation. Bone 33:259–263

    Article  CAS  PubMed  Google Scholar 

  43. Hohman EE (2014). Use of calcium isotopes for assessment of bone turnover: methodology and botanical intervention studies. Doctor of Philosophy Thesis, Purdue University

  44. Nordin BEC, Peacock M (1969) The role of the kidney in the regulation of plasma calcium. Lancet 13:1280–1283

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Nutrition Science, Purdue University, 700 W State Street, West Lafayette, IN, 47907, USA

    C. M. Weaver, B. R. Martin & M. Wastney

  2. Department of Physics, Purdue University, 525 Northwestern Ave., West Lafayette, IN, 47907-2036, USA

    G. S. Jackson

  3. Department of Statistics, Purdue University, 250 N University Street, West Lafayette, IN, 47907, USA

    G. P. McCabe

  4. Indiana University School of Medicine, Indianapolis, IN, 46223, USA

    M. Peacock

Authors
  1. C. M. Weaver
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  2. B. R. Martin
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  3. G. S. Jackson
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  4. G. P. McCabe
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  6. M. Wastney
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Correspondence to C. M. Weaver.

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Weaver, C.M., Martin, B.R., Jackson, G.S. et al. Calcium-41: a technology for monitoring changes in bone mineral. Osteoporos Int 28, 1215–1223 (2017). https://doi.org/10.1007/s00198-016-3849-3

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  • DOI: https://doi.org/10.1007/s00198-016-3849-3

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