Skip to main content

Advertisement

Log in

Vibrational Spectroscopic Imaging for the Evaluation of Matrix and Mineral Chemistry

  • Imaging (T Lang and F Wehrli, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Metabolic bone diseases manifesting fragility fractures (such as osteoporosis) are routinely diagnosed based on bone mineral density (BMD) measurements, and the effect of various therapies also evaluated based on the same outcome. Although useful, it is well recognized that this metric does not fully account for either fracture incidence or the effect of various therapies on fracture incidence, thus, the emergence of bone quality as a contributing factor in the determination of bone strength. Infrared and Raman vibrational spectroscopic techniques are particularly well-suited for the determination of bone quality as they provide quantitative and qualitative information of the mineral and organic matrix bone components, simultaneously. Through the use of microspectroscopic techniques, this information is available in a spatially resolved manner, thus, the outcomes may be easily correlated with outcomes from techniques such as histology, histomorphometry, and nanoindentation, linking metabolic status with material properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Boyce TM, Bloebaum RD. Cortical aging differences and fracture implications for the human femoral neck. Bone. 1993;14:769–78.

    PubMed  CAS  Google Scholar 

  2. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:1254–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  3. Cummings SR. Are patients with hip fractures more osteoporotic? Review of the evidence. Am J Med. 1985;78:487–94.

    PubMed  CAS  Google Scholar 

  4. McCreade RB, Goldstein AS. Biomechanics of fracture: is bone mineral density sufficient to assess risk? J Bone Miner Res. 2000;15:2305–8.

    Google Scholar 

  5. Hui S, Slemenda CW, Johnston CC. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest. 1988;81:1804–9.

    PubMed  CAS  PubMed Central  Google Scholar 

  6. Siris ES, Brenneman SK, Miller PD, Barrett-Connor E, Chen YT, Sherwood LM, et al. Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and older: results from the National Osteoporosis Risk Assessment (NORA). J Bone Miner Res. 2004;19:1215–20.

    PubMed  Google Scholar 

  7. Jepsen KJ, Schaffler MB. Bone mass does not adequately predict variations in bone fragility: a genetic approach. Trans Orthop Res Soc 47th Annual Meeting. 2001;114.

  8. Parfitt AM. Bone remodeling and bone loss: understanding the pathophysiology of osteoporosis. Clin Obstet Gynecol. 1987;30:789–811.

    PubMed  CAS  Google Scholar 

  9. Mosekilde L, Mosekilde L, Danielsen CC. Biomechanical competence of vertebral trabecular bone in relation to ash density and age in normal individuals. Bone. 1987;8(2):79–85.

    PubMed  CAS  Google Scholar 

  10. McCabe F, Zhou LJ, Steele CR, Marcus R. Noninvasive assessment of ulnar bending stiffness in women. J Bone Miner Res. 1991;6:53–9.

    PubMed  CAS  Google Scholar 

  11. Kanis JA, Melton LJI, Christiansen C, Johnston CJ, Haltaev N. Perspective: the diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–42.

    PubMed  CAS  Google Scholar 

  12. Kann P, Graeben S, Beyer J. Age-dependence of bone material quality shown by the measurement of frequency of resonance in the ulna. Calcif Tissue Int. 1994;54:96–100.

    PubMed  CAS  Google Scholar 

  13. Schnitzler CM. Bone quality: a determinant for certain risk factors for bone fragility. Calcif Tissue Int. 1993;53:S27–31.

    PubMed  Google Scholar 

  14. Ott SM. When bone mass fails to predict bone failure. Calcif Tissue Int. 1993;53(Suppl):S7–13.

    PubMed  Google Scholar 

  15. Cummings SR, Black DM, Nevitt MC, Browner WS, Cauley JA, Genant HK, et al. Appendicular bone density and age predict hip fracture in women: the study of osteoporotic fractures research group. JAMA. 1990;263:665–8.

    PubMed  CAS  Google Scholar 

  16. Gourion-Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, et al. Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res. 2009;24:1565–71.

    PubMed  PubMed Central  Google Scholar 

  17. Malluche HH, Porter DS, Mawad H, Monier-Faugere MC, Pienkowski D. Low-energy fractures without low T-scores characteristic of osteoporosis: a possible bone matrix disorder. J Bone Joint Surg Am. 2013;95:e1391–6.

    PubMed  Google Scholar 

  18. Misof BM, Gamsjaeger S, Cohen A, Hofstetter B, Roschger P, Stein E, et al. Bone material properties in premenopausal women with idiopathic osteoporosis. J Bone Miner Res. 2012;27:2551–61.

    PubMed  CAS  PubMed Central  Google Scholar 

  19. Paschalis EP, Shane E, Lyritis G, Skarantavos G, Mendelsohn R, Boskey AL. Bone fragility and collagen cross-links. J Bone Miner Res. 2004;19:2000–4.

    PubMed  PubMed Central  Google Scholar 

  20. Fratzl P, Gupta HS, Paschalis EP, Roschger P. Structure and mechanical quality of the collagen-mineral composite in bone. J Mater Chem. 2004;14:2115–23.

    CAS  Google Scholar 

  21. Einhorn TA. The bone organ system: form and function. In: Marcus R, Feldman D, Kelsey J, editors. Osteoporosis. New York: Academic Press Inc; 1996.

    Google Scholar 

  22. Boskey A, Pleshko Camacho N. FT-IR imaging of native and tissue-engineered bone and cartilage. Biomaterials. 2007;28:2465–78.

    PubMed  CAS  PubMed Central  Google Scholar 

  23. Paschalis EP. Fourier transform infrared analysis and bone. Osteoporos Int. 2009;20:1043–7.

    PubMed  CAS  Google Scholar 

  24. Paschalis EP. Fourier transform infrared imaging of bone. Methods Mol Biol. 2012;816:517–25.

    PubMed  CAS  Google Scholar 

  25. Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. 2008;42:456–66.

    PubMed  CAS  Google Scholar 

  26. Burket JC, Brooks DJ, MacLeay JM, Baker SP, Boskey AL, van der Meulen MC. Variations in nanomechanical properties and tissue composition within trabeculae from an ovine model of osteoporosis and treatment. Bone. 2013;52:326–36.

    PubMed  CAS  PubMed Central  Google Scholar 

  27. Donnelly E, Boskey AL, Baker SP, van der Meulen MC. Effects of tissue age on bone tissue material composition and nanomechanical properties in the rat cortex. J Biomed Mater Res A. 2010;92:1048–56.

    PubMed  PubMed Central  Google Scholar 

  28. Gamsjaeger S, Brozek W, Recker R, Klaushofer K, Paschalis EP. Transmenopausal changes in trabecular bone quality. J Bone Miner Res. 2013.

  29. Paschalis EP, Tatakis DN, Robins S, Fratzl P, Manjubala I, Zoehrer R, et al. Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral. Bone. 2011;49:1232–41.

    PubMed  CAS  PubMed Central  Google Scholar 

  30. Kuroda T, Tanaka S, Saito M, Shiraki Y, Shiraki M. Plasma level of homocysteine associated with severe vertebral fracture in postmenopausal women. Calcif Tissue Int. 2013;93:269–75.

    PubMed  CAS  Google Scholar 

  31. Yang J, Hu X, Zhang Q, Cao H, Wang J, Liu B. Homocysteine level and risk of fracture: a meta-analysis and systematic review. Bone. 2012;51:376–82.

    PubMed  CAS  Google Scholar 

  32. El Maghraoui A, Ghozlani I, Mounach A, Rezqi A, Oumghar K, Achemlal L, et al. Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women. J Clin Densitom. 2012;15:328–33.

    PubMed  Google Scholar 

  33. Leboff MS, Narweker R, LaCroix A, Wu L, Jackson R, Lee J, et al. Homocysteine levels and risk of hip fracture in postmenopausal women. J Clin Endocrinol Metab. 2009;94:1207–13.

    PubMed  CAS  PubMed Central  Google Scholar 

  34. McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med. 2004;350:2042–9.

    PubMed  CAS  Google Scholar 

  35. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350:2033–41.

    PubMed  Google Scholar 

  36. Jager I, Fratzl P. Mineralized collagen fibrils: a mechanical model with a staggered arrangement of mineral particles. Biophys J. 2000;79:1737–46.

    PubMed  CAS  PubMed Central  Google Scholar 

  37. Gao H, Ji B, Jager IL, Arzt E, Fratzl P. Materials become insensitive to flaws at nanoscale: lessons from nature. Proc Natl Acad Sci U S A. 2003;100:5597–600.

    PubMed  CAS  PubMed Central  Google Scholar 

  38. Bailey AJ, Wotton SF, Sims TJ, Thompson PW. Post-translational modifications in the collagen of human osteoporotic femoral head. Biochem Biophys Res Comm. 1992;185:801–5.

    PubMed  CAS  Google Scholar 

  39. Bailey AJ, Wotton SF, Sims TJ, Thompson PW. Biochemical changes in the collagen of human osteoporotic bone matrix. Connect Tissue Res. 1993;29:119–32.

    PubMed  CAS  Google Scholar 

  40. Masse PG, Rimnac CM, Yamauchi M, Coburn PS, Rucker BR, Howell SD, et al. Pyridoxine deficiency affects biomechanical properties of chick tibial bone. Bone. 1996;18:567–74.

    PubMed  CAS  Google Scholar 

  41. Oxlund H, Barckman M, Ortoft G, Andreassen TT. Reduced concentrations of collagen cross-links are associated with reduced strength of bone. Bone. 1995;17(4 Suppl):365S–71S.

    PubMed  CAS  Google Scholar 

  42. Socrates G. Infrared and Raman characteristic group frequencies: tables and charts. Chichester: Wiley; 2001.

    Google Scholar 

  43. Barer R, Cole ARH, Thompson HW. Infrared spectroscopy with the reflecting microscope in physics, chemistry, and biology. Nature. 1949;163:198–201.

    PubMed  CAS  Google Scholar 

  44. Delhaye M, Dhamelincourt. Laser Raman Microprobe and Microscope Proceeding Abstracts, Fourth International Conference on Raman Spectroscopy, Brunswick, Maine. 1974.

  45. Rosasco GJ, Etz E. Investigation of the Raman Spectra of Individual Micron Sized Particles Proceeding Abstracts, Fourth International Conference on Raman Spectroscopy, Brunswick, Maine. 1974.

  46. Raman, Infrared, and Near-Infrared Chemical Imaging. In: Sasic S, Ozaki Y editors. 2010.

  47. Emerging Biomedical and Pharmaceutical Applications of Raman Spectroscopy. In: Morris M, Matousek P, editors. Heidelberg: Springer; 2010.

  48. Evans CL, Xie XS. Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine. Ann Rev Analytic Chem. 2008;1:883–909.

  49. Levin IW, Bhargava R. Fourier transform infrared vibrational spectroscopic imaging: integrating microscopy and molecular recognition. Annu Rev Phys Chem. 2005;56:429–74.

    PubMed  CAS  Google Scholar 

  50. Lothar Opilik L, Thomas Schmid T, Zenobi R. Modern Raman imaging: vibrational spectroscopy on the micrometer and nanometer scales. Ann Rev Analytic Chemi. 2013;6:379–98.

  51. Huth F, Govyadinov A, Amarie SW, Nuansing W, Keilmann F, Hillenbrand R. Working principle of nano-FTIR -Nano-FTIR absorption spectroscopy of molecular fingerprints at 20 nm spatial resolution. Nano Lett. 2012;12:3973–8.

    PubMed  CAS  Google Scholar 

  52. Marcott C, Lo M, Kjoller K, Domanov K, Balooch G, Luengo GS. Nanoscale infrared (IR) spectroscopy and imaging of structural lipids in human stratum corneum using an atomic force microscope to directly detect absorbed light from a tunable IR laser source. Exp Dermatol. 2013;22:419–21.

    PubMed  CAS  Google Scholar 

  53. Marcott C, Lo M, Hu Q, Kjoller K, Boskey A, Noda I. Using 2D correlation analysis to enhance spectral information available from highly spatially resolved AFM-IR spectra. J Molec Struct. 2014.

  54. Pettinger B. Single-molecule surface- and tip-enhanced Raman spectroscopy. Mol Phys. 2010;108:2039–59.

    CAS  Google Scholar 

  55. Sonntag MD, Garibay LK, Roberts JM, Seideman T, Scheidt KA, Jensen L, et al. Single-molecule tip-enhanced Raman spectroscopy. J Phys Chem. 2012;116:478–83.

    CAS  Google Scholar 

  56. Saar BG, Freudiger CW, Stanley CM, Holtom GR, Xie XS. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science. 2010;330:1368–70.

    PubMed  CAS  PubMed Central  Google Scholar 

  57. Saar BG, Contreras-Rojas LR, Xie XS, Guy RH. Imaging drug delivery to skin with stimulated Raman scattering microscopy. Mol Pharm. 2011;8:969–75.

    PubMed  CAS  PubMed Central  Google Scholar 

  58. Ji M, Orringer DA, Freudiger CW, Ramkissoon S, Liu X, Lau D, et al. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci Transl Med. 2013;5:201ra119.

    PubMed  PubMed Central  Google Scholar 

  59. Draper ER, Morris MD, Camacho NP, Matousek P, Towrie M, Parker AW. Novel assessment of bone using time-resolved transcutaneous Raman spectroscopy. J Bone Miner Res. 2005;20:1968–72.

    PubMed  CAS  Google Scholar 

  60. Matousek P. Inverse spatially offset Raman spectroscopy for deep noninvasive probing of turbid media. Appl Spectrosc. 2006;60:1341–7.

    PubMed  CAS  Google Scholar 

  61. Schulmerich MV, Dooley KA, Morris MD, Vanasse TM, Goldstein SA. Transcutaneous fiber optic Raman spectroscopy of bone using annular illumination and a circular array of collection fibers. J Biomed Opt. 2006;11:060502.

    PubMed  Google Scholar 

  62. Ding H, Nyman JS, Sterling JA, Perrien DS, Mahadevan-Jansen A, Bi X. Development of Raman spectral markers to assess metastatic bone in breast cancer. J Biomed Opt. 2014;19:111606.

    PubMed  Google Scholar 

  63. Sharma B, Ma K, Glucksberg MR, Van Duyne RP. Seeing through bone with surface-enhanced spatially offset Raman spectroscopy. J Am Chem Soc. 2013;135:17290–3.

    PubMed  CAS  Google Scholar 

  64. Demers JL, Davis SC, Pogue BW, Morris MD. Multichannel diffuse optical Raman tomography for bone characterization in vivo: a phantom study. Biomed Opt Express. 2012;3:2299–305.

    PubMed  PubMed Central  Google Scholar 

  65. Okagbare PI, Begun D, Tecklenburg M, Awonusi A, Goldstein SA, Morris MD. Noninvasive Raman spectroscopy of rat tibiae: approach to in vivo assessment of bone quality. J Biomed Opt. 2012;17:90502–1.

    PubMed  Google Scholar 

  66. Okagbare PI, Esmonde-White FW, Goldstein SA, Morris MD. Development of non-invasive Raman spectroscopy for in vivo evaluation of bone graft osseointegration in a rat model. Analyst. 2010;135:3142–6.

    PubMed  CAS  PubMed Central  Google Scholar 

  67. Schulmerich MV, Cole JH, Kreider JM, Esmonde-White F, Dooley KA, Goldstein SA, et al. Transcutaneous Raman spectroscopy of murine bone in vivo. Appl Spectrosc. 2009;63:286–95.

    PubMed  CAS  PubMed Central  Google Scholar 

  68. Schulmerich MV, Cole JH, Dooley KA, Morris MD, Kreider JM, Goldstein SA. Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue. J Biomed Opt. 2008;13:021108.

    PubMed  PubMed Central  Google Scholar 

  69. Reilly DT, Burstein AH. The mechanical properties of cortical bone. JBJS. 1974;56A:1001–22.

    Google Scholar 

  70. Martin RB, Ishida J. The relative effects of collagen fiber orientation, porosity, density, and mineralization on bone strength. J Biomech. 1989;22:419–26.

    PubMed  CAS  Google Scholar 

  71. Boskey AL, Pleshko N, Doty SB, Mendelsohn R. Applications of Fourier Transform Infrared (FT-IR) Microscopy to the study of mineralization in bone and cartilage. Cells Mater. 1992;2:209–20.

    Google Scholar 

  72. Donnelly E, Chen DX, Boskey AL, Baker SP, van der Meulen MC. Contribution of mineral to bone structural behavior and tissue mechanical properties. Calcif Tissue Int. 2010;87:450–60.

    PubMed  CAS  PubMed Central  Google Scholar 

  73. Boskey AL, DiCarlo E, Paschalis E, West P, Mendelsohn R. Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. Osteoporos Int. 2005;16:2031–8.

    PubMed  CAS  PubMed Central  Google Scholar 

  74. Paschalis EP, Betts F, DiCarlo E, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of human iliac crest biopsies from untreated osteoporotic bone. Calcif Tissue Int. 1997;61:487–92.

    PubMed  CAS  Google Scholar 

  75. Durchschlag E, Paschalis EP, Zoehrer R, Roschger P, Fratzl P, Recker R, et al. Bone material properties in trabecular bone from human iliac crest biopsies after 3- and 5-year treatment with risedronate. J Bone Miner Res. 2006;21:1581–90.

    PubMed  CAS  Google Scholar 

  76. Gamsjaeger S, Buchinger B, Zoehrer R, Phipps R, Klaushofer K, Paschalis EP. Effects of one year daily teriparatide treatment on trabecular bone material properties in postmenopausal osteoporotic women previously treated with alendronate or risedronate. Bone. 2011;49:1160–5.

    PubMed  CAS  Google Scholar 

  77. Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser JA, et al. Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly zoledronic acid. J Bone Miner Res. 2011;26:12–8.

    PubMed  CAS  Google Scholar 

  78. Gamsjaeger S, Hofstetter B, Zwettler E, Recker R, Gasser JA, Eriksen EF, et al. Effects of 3 years treatment with once-yearly zoledronic acid on the kinetics of bone matrix maturation in osteoporotic patients. Osteoporos Int. 2013;24:339–47.

    PubMed  CAS  Google Scholar 

  79. Hofstetter B, Gamsjaeger S, Phipps RJ, Recker RR, Ebetino FH, Klaushofer K, et al. Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces. J Bone Miner Res. 2012;27:995–1003.

    PubMed  CAS  Google Scholar 

  80. Paschalis EP, Glass EV, Donley DW, Eriksen EF. Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. J Clin Endocrinol Metab. 2005;90:4644–9.

    PubMed  CAS  Google Scholar 

  81. Roschger P, Manjubala I, Zoeger N, Meirer F, Simon R, Li C, et al. Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment. J Bone Miner Res. 2010;25:891–900.

    PubMed  Google Scholar 

  82. Boskey AL, Spevak L, Weinstein RS. Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int. 2009;20:793–800.

    PubMed  CAS  PubMed Central  Google Scholar 

  83. Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. 2010;46:666–72.

    PubMed  CAS  PubMed Central  Google Scholar 

  84. Paschalis EP, Boskey AL, Kassem M, Eriksen EF. Effect of hormone replacement therapy on bone quality in early postmenopausal women. J Bone Miner Res. 2003;18:955–9.

    PubMed  CAS  Google Scholar 

  85. Boskey AL, Spevak L, Doty SB, Rosenberg L. Effects of bone CS-proteoglycans, DS-decorin, and DS-biglycan on hydroxyapatite formation in a gelatin gel. Calcif Tissue Int. 1997;61:298–305.

    PubMed  CAS  Google Scholar 

  86. Mochida Y, Duarte WR, Tanzawa H, Paschalis EP, Yamauchi M. Decorin modulates matrix mineralization in vitro. Biochem Biophys Res Commun. 2003;305:6–9.

    PubMed  CAS  Google Scholar 

  87. Nielsen KL, Allen MR, Bloomfield SA, Andersen TL, Chen XD, Poulsen HS, et al. Biglycan deficiency interferes with ovariectomy-induced bone loss. J Bone Miner Res. 2003;18:2152–8.

    PubMed  CAS  Google Scholar 

  88. Bi Y, Nielsen KL, Kilts TM, Yoon A, Wimer HF, Greenfield EM, et al. Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts. Bone. 2006;38:778–86.

    PubMed  CAS  Google Scholar 

  89. Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, et al. Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet. 1998;20:78–82.

    PubMed  CAS  Google Scholar 

  90. Gualeni B, de Vernejoul MC, Marty-Morieux C, De Leonardis F, Franchi M, Monti L, et al. Alteration of proteoglycan sulfation affects bone growth and remodeling. Bone. 2013;54:83–91.

    PubMed  CAS  PubMed Central  Google Scholar 

  91. Boskey AL, Maresca M, Armstrong AL, Ehrlich MG. Treatment of proteoglycan aggregates with physeal enzymes reduces their ability to inhibit hydroxyapatite proliferation in a gelatin gel. J Orthop Res. 1992;10:313–9.

    PubMed  CAS  Google Scholar 

  92. Grzesik WJ, Frazier CR, Shapiro JR, Sponseller PD, Robey PG, Fedarko NS. Age-related changes in human bone proteoglycan structure. Impact of osteogenesis imperfecta. J Biol Chem. 2002;277:43638–47.

    PubMed  CAS  Google Scholar 

  93. Sauren YM, Mieremet RH, Groot CG, Scherft JP. An electron microscopic study on the presence of proteoglycans in the mineralized matrix of rat and human compact lamellar bone. Anat Rec. 1992;232:36–44.

    PubMed  CAS  Google Scholar 

  94. Thompson WR, Modla S, Grindel BJ, Czymmek KJ, Kirn-Safran CB, Wang L, et al. Perlecan/Hspg2 deficiency alters the peri-cellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone. J Bone Miner Res. 2011;26:618–29.

    PubMed  CAS  PubMed Central  Google Scholar 

  95. Ohtsuki T, Hatake K, Suzu S, Saito K, Motoyoshi K, Miura Y. Immunohistochemical identification of proteoglycan form of macrophage colony-stimulating factor on bone surface. Calcif Tissue Int. 1995;57:213–7.

    PubMed  CAS  Google Scholar 

  96. Roughley PJ. The structure and function of cartilage proteoglycans. Eur Cell Mater. 2006;12:92–101.

    PubMed  CAS  Google Scholar 

  97. Rieppo L, Rieppo J, Jurvelin JS, Saarakkala S. Fourier transform infrared spectroscopic imaging and multivariate regression for prediction of proteoglycan content of articular cartilage. PLoS One. 2012;7:e32344.

    PubMed  CAS  PubMed Central  Google Scholar 

  98. Rieppo L, Saarakkala S, Narhi T, Holopainen J, Lammi M, Helminen HJ, et al. Quantitative analysis of spatial proteoglycan content in articular cartilage with Fourier transform infrared imaging spectroscopy: critical evaluation of analysis methods and specificity of the parameters. Microsc Res Tech. 2010;73:503–12.

    PubMed  CAS  Google Scholar 

  99. Saadat E, Lan H, Majumdar S, Rempel DM, King KB. Long-term cyclical in vivo loading increases cartilage proteoglycan content in a spatially specific manner: an infrared microspectroscopic imaging and polarized light microscopy study. Arthritis Res Ther. 2006;8:R147.

    PubMed  PubMed Central  Google Scholar 

  100. Yin JH, Xia Y, Ramakrishnan N. Depth-dependent anisotropy of proteoglycan in articular cartilage by fourier transform infrared imaging. Vib Spectrosc. 2011;57:338–41.

    PubMed  CAS  PubMed Central  Google Scholar 

  101. Gamsjaeger S, Srivastava AK, Wergedal JE, Zwerina J, Klaushofer K, Paschalis EP, et al. Altered bone material properties in HLA-B27 rats include reduced mineral to matrix ratio and altered collagen cross-links. J Bone Miner Res. 2014.

  102. Bansil R, Yannas IV, Stanley HE. Raman spectroscopy: a structural probe of glycosaminoglycans. Biochim Biophys Acta. 1978;541:535–42.

    PubMed  CAS  Google Scholar 

  103. Ellis R, Green E, Winlove C. Structural analysis of glycosaminoglycans and proteoglycans by means of Raman microspectrometry. Connect Tissue Res. 2009;50:29–36.

    PubMed  Google Scholar 

  104. Smith AJ, Singhrao SK, Newman GR, Waddington RJ, Embery G. A biochemical and immuno-electron microscopical analysis of chondroitin sulphate-rich proteoglycans in human alveolar bone. Histochem J. 1997;29:1–9.

    PubMed  CAS  Google Scholar 

  105. Boskey AL, Reddi AH. Changes in lipids during matrix: induced endochondral bone formation. Calcif Tissue Int. 1983;35:549–54.

    PubMed  CAS  Google Scholar 

  106. Goldberg M, Boskey AL. Lipids and biomineralizations. Prog Histochem Cytochem. 1996;31:1–187.

    PubMed  Google Scholar 

  107. Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology. 2005;15:16R–28R.

    PubMed  CAS  Google Scholar 

  108. Tang SY, Zeenath U, Vashishth D. Effects of non-enzymatic glycation on cancellous bone fragility. Bone. 2007;40:1144–51.

    PubMed  CAS  Google Scholar 

  109. Frushour BG, Koenig JL. Raman scattering of collagen, gelatin, and elastin. Biopolymers. 1975;14:379–91.

    PubMed  CAS  Google Scholar 

  110. Penel G, Delfosse C, Descamps M, Leroy G. Composition of bone and apatitic biomaterials as revealed by intravital Raman microspectroscopy. Bone. 2005;36:893–901.

    PubMed  CAS  Google Scholar 

  111. Gamsjaeger S, Brozek W, Recker R, Klaushofer K, Paschalis EP. Transmenopausal changes in trabecular bone quality. J Bone Miner Res. 2014;29:608–17.

    PubMed  CAS  Google Scholar 

  112. Morris MD, Mandair GS. Raman assessment of bone quality. Clin Orthop Relat Res. 2011;469:2160–9.

    PubMed  PubMed Central  Google Scholar 

  113. Gadaleta SJ, Paschalis EP, Betts F, Mendelsohn R, Boskey AL. Fourier transform infrared spectroscopy of the solution-mediated conversion of amorphous calcium phosphate to hydroxyapatite: new correlations between X-ray diffraction and infrared data. Calcif Tissue Int. 1996;58:9–16.

    PubMed  CAS  Google Scholar 

  114. Kazanci M, Fratzl P, Klaushofer K, Paschalis EP. Complementary information on in vitro conversion of amorphous (precursor) calcium phosphate to hydroxyapatite from Raman microspectroscopy and wide-angle X-ray scattering. Calcif Tissue Int. 2006;79:354–9.

    PubMed  CAS  Google Scholar 

  115. Fratzl P, Roschger P, Eschberger J, Abendroth B, Klaushofer K. Abnormal bone mineralization after fluoride treatment in osteoporosis: a small-angle x-ray-scattering study. J Bone Miner Res. 1994;9:1541–9.

    PubMed  CAS  Google Scholar 

  116. Paschalis EP, DiCarlo E, Betts F, Sherman P, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of human osteonal bone. Calcif Tissue Int. 1996;59:480–7.

    PubMed  CAS  Google Scholar 

  117. Spevak L, Flach CR, Hunter T, Mendelsohn R, Boskey A. Fourier transform infrared spectroscopic imaging parameters describing acid phosphate substitution in biologic hydroxyapatite. Calcif Tissue Int. 2013;92:418–28.

    PubMed  CAS  PubMed Central  Google Scholar 

  118. Paschalis EP, Betts F, DiCarlo E, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of normal human cortical and trabecular bone. Calcif Tissue Int. 1997;61:480–6.

    PubMed  CAS  Google Scholar 

  119. Huang RY, Miller LM, Carlson CS, Chance MR. In situ chemistry of osteoporosis revealed by synchrotron infrared microspectroscopy. Bone. 2003;33:514–21.

    PubMed  CAS  Google Scholar 

  120. Miller LM, Tibrewala J, Carlson CS. Examination of bone chemical composition in osteoporosis using fluorescence-assisted synchrotron infrared microspectroscopy. Cell Mol Biol. 2000;46:1035–44.

    PubMed  CAS  Google Scholar 

  121. Yamauchi M. Collagen: the major matrix molecule in mineralized tissues. In: Anderson JJB, Garner SC, editors. Calcium and phosphorus in health and disease. New York: CRC Press; 1996. p. 127–41.

    Google Scholar 

  122. Carden A, Rajachar RM, Morris MD, Kohn DH. Ultrastructural changes accompanying the mechanical deformation of bone tissue: a Raman imaging study. Calcif Tissue Int. 2003;72:166–75.

    PubMed  CAS  Google Scholar 

  123. Paschalis EP, Verdelis K, Doty SB, Boskey AL, Mendelsohn R, Yamauchi M. Spectroscopic characterization of collagen cross-links in bone. J Bone Miner Res. 2001;16:1821–8.

    PubMed  CAS  Google Scholar 

  124. Dong A, Huang P, Caughey WS. Protein secondary structures in water from second-derivative amide I infrared spectra. Biochemistry. 1990;29:3303–8.

    PubMed  CAS  Google Scholar 

  125. Kohler A, Bertrand D, Martens H, Hannesson K, Kirschner C, Ofstad R. Multivariate image analysis of a set of FTIR microspectroscopy images of aged bovine muscle tissue combining image and design information. Anal Bioanal Chem. 2007;389:1143–53.

    PubMed  CAS  Google Scholar 

  126. Susi H, Byler DM. Protein structure by Fourier transforms infrared spectroscopy: second derivative spectra. Biochem Biophys Res Commun. 1983;115:391–7.

    PubMed  CAS  Google Scholar 

  127. Blank RD, Baldini TH, Kaufman M, Bailey S, Gupta R, Yershov Y, et al. Spectroscopically determined collagen Pyr/deH-DHLNL cross-link ratio and crystallinity indices differ markedly in recombinant congenic mice with divergent calculated bone tissue strength. Connect Tissue Res. 2003;44:134–42.

    PubMed  CAS  Google Scholar 

  128. Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. Bonekey Rep. 2013;2:447.

    PubMed  Google Scholar 

  129. Donnelly E, Meredith DS, Nguyen JT, Gladnick BP, Rebolledo BJ, Shaffer AD, et al. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. J Bone Miner Res. 2012;27:672–8.

    PubMed  CAS  Google Scholar 

  130. Gourion-Arsiquaud S, Lukashova L, Power J, Loveridge N, Reeve J, Boskey AL. Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls. J Bone Miner Res. 2013;28:150–61.

    PubMed  CAS  PubMed Central  Google Scholar 

  131. Miller LM, Vairavamurthy V, Chance MR, Mendelsohn R, Paschalis EP, Betts F, et al. In situ analysis of mineral content and crystallinity in bone using infrared micro-spectroscopy of the nu(4) PO(4)(3-) vibration. Biochim Biophys Acta. 2001;1527:11–9.

    PubMed  CAS  Google Scholar 

  132. Cohen A, Dempster DW, Recker RR, Stein EM, Lappe JM, Zhou H, et al. Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2011;96:3095–105.

    PubMed  CAS  PubMed Central  Google Scholar 

  133. Cohen A, Dempster DW, Stein EM, Nickolas TL, Zhou H, McMahon DJ, et al. Increased marrow adiposity in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2012;97:2782–91.

    PubMed  CAS  PubMed Central  Google Scholar 

  134. Cohen A, Lang TF, McMahon DJ, Liu XS, Guo XE, Zhang C, et al. Central QCT reveals lower volumetric BMD and stiffness in premenopausal women with idiopathic osteoporosis, regardless of fracture history. J Clin Endocrinol Metab. 2012;97:4244–52.

    PubMed  CAS  PubMed Central  Google Scholar 

  135. Cohen A, Liu XS, Stein EM, McMahon DJ, Rogers HF, Lemaster J, et al. Bone microarchitecture and stiffness in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2009;94:4351–60.

    PubMed  CAS  PubMed Central  Google Scholar 

  136. Donovan MA, Dempster D, Zhou H, McMahon DJ, Fleischer J, Shane E. Low bone formation in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2005;90:3331–6.

    PubMed  CAS  Google Scholar 

  137. Liu XS, Cohen A, Shane E, Stein E, Rogers H, Kokolus SL, et al. Individual trabeculae segmentation (ITS)-based morphological analysis of high-resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis. J Bone Miner Res. 2010;25:1496–505.

    PubMed  PubMed Central  Google Scholar 

  138. Rubin MR, Schussheim DH, Kulak CA, Kurland ES, Rosen CJ, Bilezikian JP, et al. Idiopathic osteoporosis in premenopausal women. Osteoporos Int. 2005;16:526–33.

    PubMed  Google Scholar 

  139. Gamsjaeger S, Masic A, Roschger P, Kazanci M, Dunlop JW, Klaushofer K, et al. Cortical bone composition and orientation as a function of animal and tissue age in mice by Raman spectroscopy. Bone. 2010;47:392–9.

    PubMed  Google Scholar 

  140. Rey C, Shimizu M, Collins B, Glimcher MJ. Resolution-enhanced Fourier transform infrared spectroscopy study of the environment of phosphate ion in the early deposits of a solid phase of calcium phosphate in bone and enamel and their evolution with age: 2. Investigations in the nu3PO4 domain. Calcif Tissue Int. 1991;49:383–8.

    PubMed  CAS  Google Scholar 

  141. Farlay D, Panczer G, Rey C, Delmas PD, Boivin G. Mineral maturity and crystallinity index are distinct characteristics of bone mineral. J Bone Miner Metab. 2010;28:433–45.

    PubMed  PubMed Central  Google Scholar 

  142. Farlay D, Duclos ME, Gineyts E, Bertholon C, Viguet-Carrin S, Nallala J, et al. The ratio 1660/1690 cm(-1) measured by infrared microspectroscopy is not specific of enzymatic collagen cross-links in bone tissue. PLoS One. 2011;6:e28736.

    PubMed  CAS  PubMed Central  Google Scholar 

  143. Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, et al. Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. J Bone Miner Res. 2012;27:825–34.

    PubMed  CAS  Google Scholar 

  144. Schulmerich MV, Dooley KA, Vanasse TM, Goldstein SA, Morris MD. Subsurface and transcutaneous Raman spectroscopy and mapping using concentric illumination rings and collection with a circular fiber-optic array. Appl Spectrosc. 2007;61:671–8.

    PubMed  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

S. Gamsjaeger, R. Mendelsohn, A. L. Boskey, S. Gourion-Arsiquaud, K. Klaushofer, and E. P. Paschalis all declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. P. Paschalis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gamsjaeger, S., Mendelsohn, R., Boskey, A.L. et al. Vibrational Spectroscopic Imaging for the Evaluation of Matrix and Mineral Chemistry. Curr Osteoporos Rep 12, 454–464 (2014). https://doi.org/10.1007/s11914-014-0238-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-014-0238-8

Keywords

Navigation