Advertisement

Raman Spectroscopy as a Biomarker-Investigative Tool in Bone Metabolism

  • Catherine BosserEmail author
  • Agathe OgierEmail author
  • Laurianne Imbert
  • Thierry Hoc
Reference work entry
  • 841 Downloads
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)

Abstract

Bone is a living material with a composite structure that endures long and repetitive shocks caused by walking or jumping. Currently, clinical imaging modalities do not completely characterize the quality of bone. Additionally, these approaches are inadequate for detecting the earliest disease stages, for determining the age, or for verifying the treatment impact. Raman spectroscopy is an easy technique that provides a fingerprint of the chemical and structural composition of bone. Thus, it allows the determination of biomarkers for the quantification of bone quality and to qualify the evolution with physiological changes and diseases as in osteoporosis and osteogenesis imperfecta.

Keywords

Bone biomarkers Bone quality Mineralization Crystallinity Collagen maturity Osteogenesis imperfecta Osteoporosis Raman spectroscopy 

List of Abbreviations

BMD

Bone mineral density

BP

Bisphosphonate

FWMH

Full width at maximum height

GAG

Glycosaminoglycan

IR

Infrared spectroscopy

MicroCT

Micro-computed tomography

NIR

Near infrared

PCA

Principal component analysis

PG

Proteoglycan

RS

Raman spectroscopy

References

  1. Akkus O, Adar F, Schaffler MB. Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone. Bone. 2004;34:443–53.CrossRefPubMedGoogle Scholar
  2. Awonusi A, Morris MD, Tecklenburg MMJ. Carbonate assignment and calibration in the raman spectrum of apatite. Calcif Tissue Int. 2007;81:46–52.CrossRefPubMedGoogle Scholar
  3. Bailey AJ, Paul RG, Knott L. Mechanisms of maturation and ageing of collagen. Mech Ageing Dev. 1998;106:1–56.CrossRefPubMedGoogle Scholar
  4. Bansil R, Yannas IV, Stanley HE. Raman spectroscopy: a structural probe of glycosaminoglycans. Biochim Biophys Acta. 1978;541:535–42.CrossRefPubMedGoogle Scholar
  5. Bart ZR, Hammond MA, Wallace JM. Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta. Connect Tissue Res. 2014;55:4–8.CrossRefPubMedGoogle Scholar
  6. Bazin D, Chappard C, Combes C, Carpentier X, Rouzière S, André G, Matzen G, Allix M, Thiaudière D, Reguer S, et al. Diffraction techniques and vibrational spectroscopy opportunities to characterise bones. Osteoporos Int. 2009;20:1065–75.CrossRefPubMedGoogle Scholar
  7. Bi X, Patil CA, Lynch CC, Pharr GM, Mahadevan-Jansen A, Nyman JS. Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse model. J Biomech. 2011;44:297–303.CrossRefPubMedGoogle Scholar
  8. Buchwald T, Kozielski M, Szybowicz M. Determination of collagen fibers arrangement in bone tissue by using transformations of Raman spectra maps. J Spectrosc. 2012a;27:107–17.CrossRefGoogle Scholar
  9. Buchwald T, Niciejewski K, Kozielski M, Szybowicz M, Siatkowski M, Krauss H. Identifying compositional and structural changes in spongy and subchondral bone from the hip joints of patients with osteoarthritis using Raman spectroscopy. J Biomed Opt. 2012b;17:017007.CrossRefPubMedGoogle Scholar
  10. Buckley K, Kerns JG, Birch HL, Gikas PD, Parker AW, Matousek P, Goodship AE. Functional adaptation of long bone extremities involves the localized “tuning” of the cortical bone composition; evidence from Raman spectroscopy. J Biomed Opt. 2014;19:111602.CrossRefPubMedGoogle Scholar
  11. Burket J, Gourion-Arsiquaud S, Havill LM, Baker SP, Boskey AL, van der Meulen MCH. Microstructure and nanomechanical properties in osteons relate to tissue and animal age. J Biomech. 2011;44:277–84.CrossRefPubMedGoogle Scholar
  12. Burket JC, Brooks DJ, MacLeay JM, Baker SP, Boskey AL, van der Meulen MCH. Variations in nanomechanical properties and tissue composition within trabeculae from an ovine model of osteoporosis and treatment. Bone. 2013;52:326–36.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. Carretta R, Luisier B, Bernoulli D, Stussi E, Muller R, Lorenzetti S. Novel method to analyze post-yield mechanical properties at trabecular bone tissue level. J Mech Behav Biomed Mater 2013a; 20:6–18.Google Scholar
  15. Carretta R, Stussi E, Muller R, Lorenzetti S. Within subject heterogeneity in tissue-level post-yield mechanical and material properties in human trabecular bone. J Mech Behav Biomed Mater. 2013b;24:64–73.CrossRefPubMedGoogle Scholar
  16. Carretta R, Stussi E, Muller R, Lorenzetti S. Prediction of local ultimate strain and toughness of trabecular bone tissue by Raman material composition analysis. BioMed Res Int. 2015;2015:e457371.CrossRefGoogle Scholar
  17. Clasen ABS, Ruyter IE. Quantitative determination of type A and type B carbonate in human deciduous and permanent enamel by means of fourier transform infrared spectrometry. Adv Dent Res. 1997;11:523–7.CrossRefGoogle Scholar
  18. Donnelly E, Boskey AL, Baker SP, van der Meulen MCH. Effects of tissue age on bone tissue material composition and nanomechanical properties in the rat cortex. J Biomed Mater Res A. 2009;92A:1048–56.Google Scholar
  19. Dooley KA, McCormack J, Fyhrie DP, Morris MD. Stress mapping of undamaged, strained, and failed regions of bone using Raman spectroscopy. J Biomed Opt. 2009;14:044018.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Draper ER, Morris MD, Camacho NP, Matousek P, Towrie M, Parker AW, Goodship AE. Novel assessment of bone using time-resolved transcutaneous Raman spectroscopy. J Bone Miner Res. 2005;20:1968–72.CrossRefPubMedGoogle Scholar
  21. Esmonde-White KA, Esmonde-White FWL, Morris MD, Roessler BJ. Fiber-optic Raman spectroscopy of joint tissues. Analyst. 2011;136:1675–85.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Freeman JJ, Wopenka B, Silva MJ, Pasteris JD. Raman spectroscopic detection of changes in bioapatite in mouse femora as a function of age and in vitro fluoride treatment. Calcif Tissue Int. 2001;68:156–62.CrossRefPubMedGoogle Scholar
  23. Gallant MA, Brown DM, Organ JM, Allen MR, Burr DB. Reference-point indentation correlates with bone toughness assessed using whole-bone traditional mechanical testing. Bone. 2013;53:301–5.CrossRefPubMedGoogle Scholar
  24. Gamsjaeger S, Masic A, Roschger P, Kazanci M, Dunlop JWC, Klaushofer K, Paschalis EP, Fratzl P. Cortical bone composition and orientation as a function of animal and tissue age in mice by Raman spectroscopy. Bone. 2010;47:392–9.CrossRefPubMedGoogle Scholar
  25. Gamsjaeger S, Hofstetter B, Fratzl-Zelman N, Roschger P, Roschger A, Fratzl P, Brozek W, Masic A, Misof BM, Glorieux FH, et al. Pediatric reference Raman data for material characteristics of iliac trabecular bone. Bone. 2014a;69:89–97.CrossRefPubMedGoogle Scholar
  26. Gamsjaeger S, Klaushofer K, Paschalis EP. Raman analysis of proteoglycans simultaneously in bone and cartilage. J Raman Spectrosc. 2014b;45:794–800.CrossRefGoogle Scholar
  27. Gamulin O, Serec K, Bilić V, Balarin M, Kosović M, Drmić D, Brčić L, Seiwerth S, Sikirić P. Monitoring the healing process of rat bones using Raman spectroscopy. J Mol Struct. 2013;1044:308–13.CrossRefGoogle Scholar
  28. Gentleman E, Swain RJ, Evans ND, Boonrungsiman S, Jell G, Ball MD, Shean TAV, Oyen ML, Porter A, Stevens MM. Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation. Nat Mater. 2009;8:763–70.CrossRefPubMedGoogle Scholar
  29. Golcuk K, Mandair GS, Callender AF, Sahar N, Kohn DH, Morris MD. Is photobleaching necessary for Raman imaging of bone tissue using a green laser? Biochim Biophys Acta BBA Biomembr. 2006;1758:868–73.CrossRefGoogle Scholar
  30. Gong B, Mandair GS, Wehrli FW, Morris MD. Novel assessment tools for osteoporosis diagnosis and treatment. Curr Osteoporos Rep. 2014;12:357–65.CrossRefPubMedGoogle Scholar
  31. Goodyear SR, Gibson IR, Skakle JMS, Wells RPK, Aspden RM. A comparison of cortical and trabecular bone from C57 Black 6 mice using Raman spectroscopy. Bone. 2009;44:899–907.CrossRefPubMedGoogle Scholar
  32. Gupta HS, Seto J, Wagermaier W, Zaslansky P, Boesecke P, Fratzl P. Cooperative deformation of mineral and collagen in bone at the nanoscale. Proc Natl Acad Sci. 2006;103:17741–6.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hammond MA, Gallant MA, Burr DB, Wallace JM. Nanoscale changes in collagen are reflected in physical and mechanical properties of bone at the microscale in diabetic rats. Bone. 2014;60:26–32.CrossRefPubMedGoogle Scholar
  34. Hernandez CJ, Keaveny T. A biomechanical perspective on bone quality. Bone. 2006;39:1173–81.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Imbert L, Auregan JC, Pernelle K, Hoc T. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level. Bone. 2014;65:18–24.CrossRefPubMedGoogle Scholar
  36. Kavukcuoglu NB, Arteaga-Solis E, Lee-Arteaga S, Ramirez F, Mann AB. Nanomechanics and Raman spectroscopy of fibrillin 2 knock-out mouse bones. J Mater Sci. 2007;42:8788–94.CrossRefGoogle Scholar
  37. Kavukcuoglu NB, Patterson-Buckendahl P, Mann AB. Effect of osteocalcin deficiency on the nanomechanics and chemistry of mouse bones. J Mech Behav Biomed Mater. 2009;2:348–54.CrossRefPubMedGoogle Scholar
  38. Kazanci M, Roschger P, Paschalis EP, Klaushofer K, Fratzl P. Bone osteonal tissues by Raman spectral mapping: orientation–composition. J Struct Biol. 2006;156:489–96.CrossRefPubMedGoogle Scholar
  39. Kazanci M, Wagner HD, Manjubala NI, Gupta HS, Paschalis E, Roschger P, Fratzl P. Raman imaging of two orthogonal planes within cortical bone. Bone. 2007;41:456–61.CrossRefPubMedGoogle Scholar
  40. Kerns JG, Gikas PD, Buckley K, Shepperd A, Birch HL, McCarthy I, Miles J, Briggs TWR, Keen R, Parker AW, et al. Evidence from Raman spectroscopy of a putative link between inherent bone matrix chemistry and degenerative joint disease. Arthritis Rheum. 2014;66:1237–46.CrossRefGoogle Scholar
  41. Kim G, Boskey AL, Baker SP, van der Meulen MCH. Improved prediction of rat cortical bone mechanical behavior using composite beam theory to integrate tissue level properties. J Biomech. 2012;45:2784–90.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Kim G, Cole JH, Boskey AL, Baker SP, van der Meulen MC. Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone. Calcif Tissue Int. 2014;95:125–31.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Knott L, Bailey AJ. Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. Bone. 1998;22:181–7.CrossRefPubMedGoogle Scholar
  44. Kohn DH, Sahar ND, Wallace JM, Golcuk K, Morris MD. Exercise alters mineral and matrix composition in the absence of adding new bone. Cells Tissues Organs. 2008;189:33–7.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Kozielski M, Buchwald T, Szybowicz M, Błaszczak Z, Piotrowski A, Ciesielczyk B. Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping. J Mater Sci Mater Med. 2011;22:1653–61.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lieber CA, Mahadevan-Jansen A. Automated method for subtraction of fluorescence from biological Raman spectra. Appl Spectrosc. 2003;57:1363–7.CrossRefPubMedGoogle Scholar
  47. Mandair GS, Morris MD. Contributions of Raman spectroscopy to the understanding of bone strength. BoneKEy Rep. 2015;4:620.CrossRefPubMedPubMedCentralGoogle Scholar
  48. McCreadie BR, Morris MD, Chen T, Sudhaker Rao D, Finney WF, Widjaja E, Goldstein SA. Bone tissue compositional differences in women with and without osteoporotic fracture. Bone. 2006;39:1190–5.CrossRefPubMedGoogle Scholar
  49. Meganck JA, Begun DL, McElderry JD, Swick A, Kozloff KM, Goldstein SA, Morris MD, Marini JC, Caird MS. Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta. Bone. 2013;56:204–12.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Morris MD, Mandair GS. Raman assessment of bone quality. Clin Orthop Relat Res. 2011;469:2160–9.CrossRefPubMedGoogle Scholar
  51. Nalla RK, Kruzic JJ, Kinney JH, Balooch M, Ager III JW, Ritchie RO. Role of microstructure in the aging-related deterioration of the toughness of human cortical bone. Mater Sci Eng C. 2006;26:1251–60.CrossRefGoogle Scholar
  52. Newman CL, Moe SM, Chen NX, Hammond MA, Wallace JM, Nyman JS, Allen MR. Cortical bone mechanical properties are altered in an animal model of progressive chronic kidney disease. PLoS One. 2014;9:e99262.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Nyman JS, Makowski AJ, Patil CA, Masui TP, O’Quinn EC, Bi X, Guelcher SA, Nicollela DP, Mahadevan-Jansen A. Measuring differences in compositional properties of bone tissue by confocal Raman spectroscopy. Calcif Tissue Int. 2011;89:111–22.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Ojanen X, Isaksson H, Töyräs J, Turunen MJ, Malo MKH, Halvari A, Jurvelin JS. Relationships between tissue composition and viscoelastic properties in human trabecular bone. J Biomech. 2015;48:269–75.CrossRefPubMedGoogle Scholar
  55. Orkoula MG, Vardaki MZ, Kontoyannis CG. Study of bone matrix changes induced by osteoporosis in rat tibia using Raman spectroscopy. Vib Spectrosc. 2012;63:404–8.CrossRefGoogle Scholar
  56. 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.CrossRefPubMedGoogle Scholar
  57. Pinheiro ALB, Soares LGP, Marques AMC, Aciole JMS, de Souza RA, Silveira L. Raman ratios on the repair of grafted surgical bone defects irradiated or not with laser (λ780 nm) or LED (λ850 nm). J Photochem Photobiol B. 2014;138:146–54.CrossRefPubMedGoogle Scholar
  58. Ramasamy JG, Akkus O. Local variations in the micromechanical properties of mouse femur: the involvement of collagen fiber orientation and mineralization. J Biomech. 2007;40:910–8.CrossRefPubMedGoogle Scholar
  59. Rho J-Y, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierachical structure of bone. Med Eng Phys. 1998;20:92–102.CrossRefPubMedGoogle Scholar
  60. Roschger A, Gamsjaeger S, Hofstetter B, Masic A, Blouin S, Messmer P, Berzlanovich A, Paschalis EP, Roschger P, Klaushofer K, et al. Relationship between the v2PO4/amide III ratio assessed by Raman spectroscopy and the calcium content measured by quantitative backscattered electron microscopy in healthy human osteonal bone. J Biomed Opt. 2014;19:065002.CrossRefPubMedGoogle Scholar
  61. Shen J, Fan L, Yang J, Shen AG, Hu JM. A longitudinal Raman microspectroscopic study of osteoporosis induced by spinal cord injury. Osteoporos Int. 2010;21:81–7.CrossRefPubMedGoogle Scholar
  62. Silva MJ, Brodt MD, Wopenka B, Thomopoulos S, Williams D, Wassen MH, Ko M, Kusano N, Bank RA. Decreased collagen organization and content are associated with reduced strength of demineralized and intact bone in the SAMP6 mouse. J Bone Miner Res. 2006;21:78–88.CrossRefPubMedGoogle Scholar
  63. Tarnowski CP, Ignelzi MA, Morris MD. Mineralization of developing mouse calvaria as revealed by Raman microspectroscopy. J Bone Miner Res. 2002;17:1118–26.CrossRefPubMedGoogle Scholar
  64. Timlin JA, Carden A, Morris MD. Chemical microstructure of cortical bone probed by Raman transects. Appl Spectrosc. 1999;53:1429–35.CrossRefGoogle Scholar
  65. Timlin JA, Carden A, Morris MD, Rajachar RM, Kohn DH. Raman spectroscopic imaging markers for fatigue-related microdamage in bovine bone. Anal Chem. 2000;72:2229–36.CrossRefPubMedGoogle Scholar
  66. Turunen MJ, Saarakkala S, Rieppo L, Helminen HJ, Jurvelin JS, Isaksson H. Comparison between infrared and Raman spectroscopic analysis of maturing rabbit cortical bone. Appl Spectrosc. 2011;65:595–603.CrossRefPubMedGoogle Scholar
  67. Wallace JM, Golcuk K, Morris MD, Kohn DH. Inbred strain-specific effects of exercise in wild type and biglycan deficient mice. Ann Biomed Eng. 2009;38:1607–17.CrossRefPubMedPubMedCentralGoogle Scholar
  68. Wang C, Wang Y, Huffman NT, Cui C, Yao X, Midura S, Midura RJ, Gorski JP. Confocal laser Raman microspectroscopy of biomineralization foci in UMR 106 osteoblastic cultures reveals temporally synchronized protein changes preceding and accompanying mineral crystal deposition. J Biol Chem. 2009;284:7100–13.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Yamamoto T, Uchida K, Naruse K, Suto M, Urabe K, Uchiyama K, Suto K, Moriya M, Itoman M, Takaso M. Quality assessment for processed and sterilized bone using Raman spectroscopy. Cell Tissue Bank. 2012;13:409–14.CrossRefPubMedGoogle Scholar
  70. Yao X, Carleton SM, Kettle AD, Melander J, Phillips CL, Wang Y. Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model. Ann Biomed Eng. 2013;41:1139–49.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Yavorskyy A, Hernandez-Santana A, McCarthy G, McMahon G. Detection of calcium phosphate crystals in the joint fluid of patients with osteoarthritis – analytical approaches and challenges. Analyst. 2008;133:302–18.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Yeni YN, Yerramshetty J, Akkus O, Pechey C, Les CM. Effect of fixation and embedding on Raman spectroscopic analysis of bone tissue. Calcif Tissue Int. 2006;78:363–71.CrossRefPubMedGoogle Scholar
  73. Yerramshetty JS, Akkus O. The associations between mineral crystallinity and the mechanical properties of human cortical bone. Bone. 2008;42:476–82.CrossRefPubMedGoogle Scholar
  74. Yerramshetty JS, Lind C, Akkus O. The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade. Bone. 2006;39:1236–43.CrossRefPubMedGoogle Scholar
  75. Yerramshetty J, Kim D-G, Yeni YN. Increased microstructural variability is associated with decreased structural strength but with increased measures of structural ductility in human vertebrae. J Biomech Eng. 2009;131:094501.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Zhao J, Lui H, McLean DI, Zeng H. Automated autofluorescence background subtraction algorithm for biomedical Raman spectroscopy. Appl Spectrosc. 2007;61:1225–32.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Ingénierie et Vieillissement des Tissus VivantsCentrale Innovation, Centre Scientifique Auguste MoirouxEcully CedexFrance
  2. 2.UMR CNRS 5513, Laboratoire de Tribologie et Dynamique des SystèmesEcole Centrale de LyonEcully CedexFrance

Personalised recommendations