Annals of Biomedical Engineering

, Volume 33, Issue 1, pp 79–86 | Cite as

Nuclear Magnetic Resonance Studies of Bone Water

Article

Abstract

Mineralized bone tissue has a significant water component. Bone water is associated with the collagen fibers or mineral fraction or occurring as pore water of the Haversian and lacuno–canalicular system. Among the multiple physiologic functions that include signaling and providing to bone its viscoelastic properties, bone water enables the transport of ions and nutrients to and waste products from the cells. In addition, it plays a key role during mineralization whereby collagen-bound water is gradually replaced by calcium apatite-like mineral. In this review it is shown how nuclear magnetic resonance (NMR) allows the study of various physiologically relevant properties of bone water nondestructively. Isotope exchange experiments are described from which the apparent water diffusion coefficient can be calculated. The method is based on monitoring the migration of H2O into the D2O after immersion of the specimen in heavy water. Data obtained from rabbit cortical bone in the normal and mineral-depleted skeleton provide evidence for the hypothesized reciprocal relationship between bone water and mineral. Further, from the diffusion coefficient (Da = (7.8 ± 1.5) × 10−7 cm2/s) measured at 40°C it can be inferred that diffusive transport of small molecules from the bone’s microvascular system to the osteocytes occurs within minutes. Finally, whereas isotope exchange is not feasible in vivo, it is shown that bone water can be imaged by proton MRI.

Nuclear magnetic resonance Bone water Mineralization Diffusion Imaging 

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References

  1. 1.
    Ackerman, J. L., D. P. Raleigh, and M. J. Glimcher. Phosphorus-31 magnetic resonance imaging of hydroxyapatite: A model for bone imaging. Magn. Reson. Med. 25:11–11, 1992.Google Scholar
  2. 2.
    Ayasaka, N., T. Kondo, T. Goto, M. A. Kido, E. Nagata, and T. Tanaka. Differences in the transport systems between cementocytes and osteocytes in rats using microperoxidase as a tracer. Arch. Oral. Biol. 37:5363–369, 1992.CrossRefGoogle Scholar
  3. 3.
    Basha, B., D. S. Rao, Z. H. Han, and A. M. Parfitt. Osteomalacia due to vitamin D depletion: A neglected consequence of intestinal malabsorption. Am. J. Med. 108:4296–300, 2000.CrossRefGoogle Scholar
  4. 4.
    Boivin, G. Y., P. M. Chavassieux, A. C. Santora, J. Yates, and P. J. Meunier. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:5687–694, 2000.CrossRefPubMedGoogle Scholar
  5. 5.
    Borgia, G. C., R. J. Brown, and P. Fantazzini. Examples of marginal resolution of NMR relaxation peaks using UPEN and diagnostics. Magn. Reson. Imaging 19(3–4):473–475, 2001.CrossRefGoogle Scholar
  6. 6.
    Brommage, R., S. C. Miller, C. B. Langman, R. Bouillon, R. Smith, and J. E. Bourdeau. The effects of chronic vitamin D deficiency on the skeleton in the adult rabbit. Bone 9:3131–139, 1988.CrossRefGoogle Scholar
  7. 7.
    Brown, C. E., J. H. Battocletti, R. Srinivasan, J. R. Allaway, J. Moore, and P. Sigmann. In vivo 31P nuclear magnetic resonance spectroscopy of bone mineral for evaluation of osteoporosis. Clin. Chem. 34:71431–1438, 1988.Google Scholar
  8. 8.
    Brown, C. E., J. R. Allaway, K. L. Brown, and J. H. Battocletti. Noninvasive evaluation of mineral content of bone without use of ionizing radiation. Clin. Chem. 33(2 Pt 1):227–236, 1987.Google Scholar
  9. 9.
    Cho, G., Y. Wu, and J. L. Ackerman. Detection of hydroxyl ions in bone mineral by solid-state NMR spectroscopy. Science 300:56221123–1127, 2003.CrossRefPubMedGoogle Scholar
  10. 10.
    Cho, Z. H., and Y. M. Ro. Multipoint K-space point mapping (KPM) technique for NMR microscopy. Magn. Reson. Med. 32:2258–262, 1994.Google Scholar
  11. 11.
    Crank, J. The Mathematics of Diffusion, 2nd ed. London: Oxford University Press, 1957, pp. 347.Google Scholar
  12. 12.
    Currey, J. D. The mechanical consequences of variations in the mineral content of bone. J. Biomech. 2:1–11, 1969.CrossRefGoogle Scholar
  13. 13.
    Dillaman, R. M., R. D. Roer, and D. M. Gay. Fluid movement in bone: Theoretical and empirical. J. Biomech. 24(S1):163–177, 1991.CrossRefGoogle Scholar
  14. 14.
    Edelman, I. S., A. H. James, H. Baden, and F. D. Moore. Electrolyte composition of bone and the penetration of radiosodium and deuterium oxide into dog and human bone. J. Clin. Invest. 33:122–131, 1954.CrossRefGoogle Scholar
  15. 15.
    Emid, S., and J. H. N. Creyghton. High resolution NMR imaging in solids. Phys. B 128:81, 1985.Google Scholar
  16. 16.
    Fantazzini, P., R. J. Brown, and G. C. Borgia. Bone tissue and porous media: Common features and differences studied by NMR relaxation. Magn. Reson. Imaging 21(3–4):227–234, 2003.CrossRefGoogle Scholar
  17. 17.
    Fantazzini, P., R. Viola, S. M. Alnaimi, and J. H. Strange. Combined MR-relaxation and MR-cryoporometry in the study of bone microstructure. Magn. Reson. Imaging 19(3–4):481–484, 2001.CrossRefGoogle Scholar
  18. 18.
    Fernandez-Seara, M., S. L. Wehrli, M. Takahashi, and F. W. Wehrli. Water content measured by proton-deuteron exchange NMR predicts bone mineral density and mechanical properties. J. Bone Miner. Res. 19:2289–296, 2004.Google Scholar
  19. 19.
    Fernandez-Seara, M., S. L. Wehrli, and F. W. Wehrli. Diffusion of exchangeable water in cortical bone studied by nuclear magnetic resonance. Biophys. J. 82:522–529, 2002.CrossRefGoogle Scholar
  20. 20.
    Fernandez-Seara, M., S. L. Wehrli, and F. W. Wehrli. Multipoint mapping for imaging of semisolid materials. J. Magn. Reson. 160:144–150, 2003.CrossRefGoogle Scholar
  21. 21.
    Garner, E., R. Lakes, T. Lee, C. Swan, and R. Brand Viscoelastic dissipation in compact bone: implications for stress-induced fluid flow in bone. J. Biomech. Eng. 122:2166–172, 2000.CrossRefGoogle Scholar
  22. 22.
    Gravina, S., and D. G. Cory. Sensitivity and resolution of constant-time imaging. J. Magn. Reson. 104:53–61, 1994.CrossRefGoogle Scholar
  23. 23.
    Knothe Tate, M. L., U. Knothe, and P. Niederer. Experimental elucidation of mechanical load-induced fluid flow and its potential role in bone metabolism and functional adaptation. Am. J. Med. Sci. 316:3189–195, 1998.CrossRefGoogle Scholar
  24. 24.
    Lindgren, J. U., H. F. DeLuca, and R. B. Mazess. Effects of 1,25(OH)2D3 on bone tissue in the rabbit: Studies on fracture healing, disuse osteoporosis, and prednisone osteoporosis. Calcif. Tissue Int. 36:591–595, 1984.Google Scholar
  25. 25.
    Martin, R. B., and D. B. Burr. Structure, Function, and Adaptation of Compact Bone. New York: Raven Press.Google Scholar
  26. 26.
    Meunier, P. J., and G. Boivin. Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone 21:5373–377, 1997.CrossRefPubMedGoogle Scholar
  27. 27.
    Moore, J., L. Garrido, and J. Ackerman. Solid-state 31P magnetic resonance imaging of bone mineral. Magn. Reson. Med. 33:293–299, 1995.Google Scholar
  28. 28.
    Moreno, E. C., and E. J. Burke. A diaphragm cell and the procedure for studying isothermal diffusion in dental enamel. Arch. Oral. Biol. 19:5417–420, 1974.CrossRefGoogle Scholar
  29. 29.
    Myers, T. J., J. H. Battocletti, M. Mahesh, M. Gulati, C. R. Wilson, F. Pintar, and J. Reinartz. Comparison of nuclear magnetic resonance spectroscopy with dual-photon absorptiometry and dual-energy X-ray absorptiometry in the measurement of thoracic vertebral bone mineral density: Compressive force versus bone mineral. Osteoporos. Int. 4:3129–137, 1994.Google Scholar
  30. 30.
    Neuman, W. F., and M. W. Neuman. Skeletal Dynamics the Chemical Dynamics of Bone Mineral. Chicago: Univ. of Chicago Press, 1958, pp. 101.Google Scholar
  31. 31.
    Neuman, W. F., and M. W. Neuman. Studies of diffusion in calvaria. Calcif. Tissue Int. 33:4441–444, 1981.MathSciNetGoogle Scholar
  32. 32.
    Nuzzo, S. M. H. Lafage-Proust, E. Martin-Badosa, G. Boivin, T. Thomas, C. Alexandre, and F. Peyrin. Synchrotron radiation microtomography allows the analysis of three-dimensional microarchitecture and degree of mineralization of human iliac crest biopsy specimens: Effects of etidronate treatment. J. Bone Miner. Res. 17:81372–1382, 2002.Google Scholar
  33. 33.
    Paschalis, E. P., A. L. Boskey, M. Kassem, and E. F. Eriksen. Effect of hormone replacement therapy on bone quality in early postmenopausal women. J. Bone Miner. Res. 18:6955–959, 2003.Google Scholar
  34. 34.
    Robinson, R. A., and S. R. Elliot. The water content of bone. J. Bone Joint Surg. 39A:167–188, 1957.Google Scholar
  35. 35.
    Robinson, R. F. An electron-microscopy study of the crystalline inorganic component of bone and its relationship to the organic matrix. J. Bone Joint Surg. 34-A(2):389–435, 1952.Google Scholar
  36. 36.
    Robson, M. D., P. D. Gatehouse, M. Bydder, and G. M. Bydder. Magnetic resonance: An introduction to ultrashort TE (UTE) imaging. J. Comput. Assist. Tomogr. 27:6825–846, 2003.CrossRefGoogle Scholar
  37. 37.
    Stejskal, E. O. Spin diffusion measurements: Spin echoes in the presence of a time-dependent field gradient. J. Chem. Phys. 42:288–292, 1965.CrossRefGoogle Scholar
  38. 38.
    Takahashi, M., F. W. Wehrli, L. Hilaire, B. S. Zemel, and S. N. Hwang. In vivo NMR microscopy allows short-term serial assessment of multiple skeletal implications of corticosteroid exposure. Proc. Natl. Acad. Sci. USA 19:19, 2002.Google Scholar
  39. 39.
    Tate, M. L., and U. Knothe. An ex vivo model to study transport processes and fluid flow in loaded bone. J. Biomech. 33:2247–254, 2000.CrossRefGoogle Scholar
  40. 40.
    Tate, M. L., P. Niederer, and U. Knothe. In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone 22:2107–117, 1998.CrossRefGoogle Scholar
  41. 41.
    Timmins, P. A., and J. C. Wall. Bone water. Calcif. Tissue Res. 23:11–5, 1977.Google Scholar
  42. 42.
    Van der Graaf, E. R., and J. J. ten Bosch. The uptake of water by freeze-dried human dentine sections. Arch. Oral. Biol. 35:9731–739, 1990.CrossRefGoogle Scholar
  43. 43.
    Van Rietbergen, B., R. Huiskes, F. Eckstein, and P. Ruegsegger . Trabecular bone tissue strains in the healthy and osteoporotic human femur. J. Bone Miner. Res. 18:101781–1788, 2003.Google Scholar
  44. 44.
    Vose, G., and A. Kubala. Bone strength—its relationship to X-ray determined ash content. Hum. Biol. 31:262–270, 1959.Google Scholar
  45. 45.
    Wang, X., and Q. Ni. Determination of cortical bone porosity and pore size distribution using a low field pulsed NMR approach. J. Orthop. Res. 21:2312–319, 2003.CrossRefGoogle Scholar
  46. 46.
    Wu, D. D., R. D. Boyd, T. J. Fix, and D. B. Burr. Regional patterns of bone loss and altered bone remodeling in response to calcium deprivation in laboratory rabbits. Calcif. Tissue Int. 47:118–23, 1990.Google Scholar
  47. 47.
    Wu, Y., D. A. Chesler, M. J. Glimcher, L. Garrido, J. Wang, H. J. Jiang, and J. L. Ackerman. Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates. Proc. Natl. Acad. Sci. USA 96:41574–1578, 1999.CrossRefGoogle Scholar
  48. 48.
    Wu, Y., J. L. Ackerman, D. A. Chesler, J. Li, R. M. Neer, J. Wang, and M. J. Glimcher. Evaluation of bone mineral density using three-dimensional solid state phosphorus-31 NMR projection imaging. Calcif. Tissue Int. 62:6512–518, 1998.CrossRefGoogle Scholar
  49. 49.
    Wu, Y., M. J. Glimcher, C. Rey, and J. L. Ackerman. A unique protonated phosphate group in bone mineral not present in synthetic calcium phosphates. Identification by phosphorus-31 solid state NMR spectroscopy. J. Mol. Biol. 244:423–435, 1994.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2005

Authors and Affiliations

  • Felix W. Wehrli
    • 1
    • 2
  • María A. Fernández-Seara
    • 1
  1. 1.Laboratory for Structural NMR Imaging, Department of RadiologyUniversity of Pennsylvania Medical CenterPA
  2. 2.Department of RadiologyUniversity of Pennsylvania Medical CenterPA

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