Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Orthopaedics and Related Research®
Published in: Clinical Orthopaedics and Related Research® 8/2011

01-08-2011 | Symposium: Bone Quality: From Bench to Bedside

Raman Assessment of Bone Quality

Authors: Michael D. Morris, PhD, Gurjit S. Mandair, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 8/2011

Login to get access

Abstract

Background

Progress in the diagnosis and prediction of fragility fractures depends on improvements to the understating of the compositional contributors of bone quality to mechanical competence. Raman spectroscopy has been used to evaluate alterations to bone composition associated with aging, disease, or injury.

Questions/purposes

In this survey we will (1) review the use of Raman-based compositional measures of bone quality, including mineral-to-matrix ratio, carbonate-to-phosphate ratio, collagen quality, and crystallinity; (2) review literature correlating Raman spectra with biomechanical and other physiochemical measurements and with bone health; and (3) discuss prospects for ex vivo and in vivo human subject measurements.

Methods

ISI Web of Science was searched for references to bone Raman spectroscopy in peer-reviewed journals. Papers from other topics have been excluded from this review, including those on pharmaceutical topics, dental tissue, tissue engineering, stem cells, and implant integration.

Results

Raman spectra have been reported for human and animal bone as a function of age, biomechanical status, pathology, and other quality parameters. Current literature supports the use of mineral-to-matrix ratio, carbonate-to-phosphate ratio, and mineral crystallinity as measures of bone quality. Discrepancies between reports arise from the use of band intensity ratios rather than true composition ratios, primarily as a result of differing collagen band selections.

Conclusions

Raman spectroscopy shows promise for evaluating the compositional contributors of bone quality in ex vivo specimens, although further validation is still needed. Methodology for noninvasive in vivo assessments is still under development.
Literature
1.
Ager JW, Nalla RK, Balooch G, Kim G, Pugach M, Habelitz S, Marshall GW, Kinney JH, Ritchie RO. On the increasing fragility of human teeth with age: a deep-UV resonance Raman study. J Bone Miner Res. 2006;21:1879–1887.PubMedCrossRef
2.
Ager JW, Nalla RK, Breeden KL, Ritchie RO. Deep-ultraviolet Raman spectroscopy study of the effect of aging on human cortical bone. J Biomed Opt. 2005;10:034012.PubMedCrossRef
3.
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;34:443–453.PubMedCrossRef
4.
Aparicio S, Doty SB, Camacho NP, Paschalis EP, Spevak L, Mendelsohn R, Boskey AL. Optimal methods for processing mineralized tissues for Fourier transform infrared microspectroscopy. Calcif Tissue Int. 2002;70:422–429.PubMedCrossRef
5.
Awonusi A, Morris MD, Tecklenburg MM. Carbonate assignment and calibration in the Raman spectrum of apatite. Calcif Tissue Int. 2007;81:46–52.PubMedCrossRef
6.
Barth HD, Launey ME, MacDowell AA, Ager JW, Ritchie RO. On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone. Bone. 2010;46:1475–1485.PubMedCrossRef
7.
Bazin D, Chappard C, Combes C, Carpentier X, Rouziere S, Andre G, Matzen G, Allix M, Thiaudiere D, Reguer S, Jungers P, Daudon M. Diffraction techniques and vibrational spectroscopy opportunities to characterise bones. Osteoporosis Int. 2009;20:1065–1075.CrossRef
8.
Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR. The skeletal attachment of tendons—tendon ‘entheses.’ Comp Biochem Physiol A Mol Integr Physiol. 2002;133:931–945.PubMedCrossRef
9.
Beraudi A, Stea S, Bordini B, Baleani M, Viceconti M. Osteon classification in human fibular shaft by circularly polarized light. Cells Tissues Organs. 2010;191:260–268.PubMedCrossRef
10.
Blake GM, Fogelman I. How important are BMD accuracy errors for the clinical interpretation of DXA scans? J Bone Miner Res. 2008;23:457–462.PubMedCrossRef
11.
Boskey A. Bone mineral crystal size. Osteoporos Int. 2003;14(Suppl 5):S16–S20.
12.
Boskey A, Mendelsohn R. Infrared analysis of bone in health and disease. J Biomed Opt. 2005;10:031102.PubMedCrossRef
13.
Callender AF, Finney WF, Morris MD, Sahar ND, Kohn DH, Kozloff KM, Goldstein SA. Dynamic mechanical testing system for Raman microscopy of bone tissue specimens. Vibrational Spectroscopy. 2005;38:101–105.CrossRef
14.
Carden A, Morris MD. Application of vibrational spectroscopy to the study of mineralized tissues (review). J Biomed Opt. 2000;5:259–268.PubMedCrossRef
15.
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;72:166–175.PubMedCrossRef
16.
Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. 2002;288:1889–1897.PubMedCrossRef
17.
de Carmejane O, Morris MD, Davis MK, Stixrude L, Tecklenburg M, Rajachar RM, Kohan DH. Bone chemical structure response to mechanical stress studied by high pressure Raman spectroscopy. Calcif Tissue Int. 2005;76:207–213.PubMedCrossRef
18.
de Mul FFM, Otto C, Greve J, Arends J, ten Bosch JJ. Calculation of the Raman line broadening on carbonation in synthetic hydroxyapatite. J Raman Spectrosc. 1988;19:13–21.CrossRef
19.
Dendramis AL, Poser JW, Schwinn EW. Laser Raman spectroscopy of calf bone Gla protein. Biochim Biophys Acta. 1983;742:525–529.PubMedCrossRef
20.
Denson SC, Pommier CJS, Denton MB. The impact of array detectors on Raman spectroscopy. J Chem Educ. 2007;84:67.CrossRef
21.
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;92:1048–1056.PubMed
22.
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.PubMedCrossRef
23.
Faibish D, Ott SM, Boskey AL. Mineral changes in osteoporosis: a review. Clin Orthop Relat Res. 2006;443:28–38.PubMedCrossRef
24.
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;68:156–162.PubMedCrossRef
25.
Gamsjaeger S, Roschger P, Klaushofer K, Paschalis EP, Fratzl P. Cortical bone orientation and composition in a mouse model as a function of tissue age vs animal age. Bone. 2009;44(Suppl 2):S269–S270.CrossRef
26.
Genin GM, Kent A, Birman V, Wopenka B, Pasteris JD, Marquez PJ, Thomopoulos S. Functional grading of mineral and collagen in the attachment of tendon to bone. Biophys J. 2009;97:976–985.PubMedCrossRef
27.
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. 2006;1758:868–873.PubMedCrossRef
28.
Goodyear SR, Gibson IR, Skakle JM, Wells RP, Aspden RM. A comparison of cortical and trabecular bone from C57 black 6 mice using Raman spectroscopy. Bone. 2009;44:899–907.PubMedCrossRef
29.
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;46:666–672.PubMedCrossRef
30.
Gourion-Arsiquaud S, Burket JC, Havill LM, DiCarlo E, Doty SB, Mendelsohn R, van der Meulen MC, Boskey AL. Spatial variation in osteonal bone properties relative to tissue and animal age. J Bone Miner Res. 2009;24:1271–1281.PubMedCrossRef
31.
Gupta HS, Stachewicz U, Wagermaier W, Roschger P, Wagner HD, Fratzl P. Mechanical modulation at the lamellar level in osteonal bone. J Mater Res. 2006;21:1913–1921.CrossRef
32.
Hofmann T, Heyroth F, Meinhard H, Franzel W, Raum K. Assessment of composition and anisotropic elastic properties of secondary osteon lamellae. J Biomech. 2006;39:2282–2294.PubMedCrossRef
33.
Jiang SD, Jiang LS, Dai LY. Mechanisms of osteoporosis in spinal cord injury. Clin Endocrinol (Oxf). 2006;65:555–565.CrossRef
34.
Judex S, Boyd S, Qin Y-X, Miller L, Müller R, Rubin C. Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue. Curr Osteoporos Rep. 2003;1:11–19.PubMedCrossRef
35.
Kavukcuoglu NB, Denhardt DT, Guzelsu N, Mann AB. Osteopontin deficiency and aging on nanomechanics of mouse bone. J Biomed Mater Res A. 2007;83:136–144.PubMed
36.
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;2:348–354.PubMedCrossRef
37.
Kazanci M, Roschger P, Paschalis EP, Klaushofer K, Fratzl P. Bone osteonal tissues by Raman spectral mapping: orientation-composition. J Struct Biol. 2006;156:489–496.PubMedCrossRef
38.
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;41:456–461.PubMedCrossRef
39.
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. 2009;189:33-37.PubMedCrossRef
40.
Krafft C, Codrich D, Pelizzo G, Sergo V. Raman and FTIR microscopic imaging of colon tissue: a comparative study. J Biophotonics. 2008;1:154–169.PubMedCrossRef
41.
Lakshmi RJ, Alexander M, Kurien J, Mahato KK, Kartha VB. Osteoradionecrosis (ORN) of the mandible: a laser Raman spectroscopic study. Appl Spectrosc. 2003;57:1100–1116.PubMedCrossRef
42.
Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, Kinney JH, Bonewald LF. Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res. 2006;21:466–476.PubMedCrossRef
43.
Legros R, Balmain N, Bonel G. Age-related changes in mineral of rat and bovine cortical bone. Calcif Tissue Int. 1987;41:137–144.PubMedCrossRef
44.
Matousek P, Draper ER, Goodship AE, Clark IP, Ronayne KL, Parker AW. Noninvasive Raman spectroscopy of human tissue in vivo. Appl Spectrosc. 2006;60:758–763.PubMedCrossRef
45.
Matousek P, Stone N. Emerging concepts in deep Raman spectroscopy of biological tissue. Analyst. 2009;134:1058–1066.PubMedCrossRef
46.
Matsumoto Y, Mikuni-Takagaki Y, Kozai Y, Miyagawa K, Naruse K, Wakao H, Kawamata R, Kashima I, Sakurai T. Prior treatment with vitamin K(2) significantly improves the efficacy of risedronate. Osteoporos Int. 2009;20:1863–1872.PubMedCrossRef
47.
McCreadie BR, Goldstein SA. Biomechanics of fracture: is bone mineral density sufficient to assess risk? J Bone Miner Res. 2000;15:2305–2308.PubMedCrossRef
48.
McCreadie BR, Morris MD, Chen TC, Sudhaker Rao D, Finney WF, Widjaja E, Goldstein SA. Bone tissue compositional differences in women with and without osteoporotic fracture. Bone. 2006;39:1190–1195.PubMedCrossRef
49.
Mendelsohn R, Paschalis EP, Boskey AL. Infrared spectroscopy, microscopy, and microscopic imaging of mineralizing tissues: spectra-structure correlations from human iliac crest biopsies. J Biomed Opt. 1999;4:14–21.CrossRef
50.
Morris MD, Crane NJ, Gomez LE, Ignelzi MA. Compatibility of staining protocols for bone tissue with Raman imaging. Calcif Tissue Int. 2004;74:86–94.PubMedCrossRef
51.
Morris MD, Finney WF, Rajachar RM, Kohn DH. Bone tissue ultrastructural response to elastic deformation probed by Raman spectroscopy. Faraday Discuss. 2004;126:159–168; discussion 169–183.PubMedCrossRef
52.
Parkesh R, Mohsin S, Lee TC, Gunnlaugsson TC. Histological, spectroscopic, and surface analysis of microdamage in bone: toward real-time analysis using fluorescent sensors. Chem Mater. 2007;19:1656–1663.CrossRef
53.
Paschalis EP, DiCarlo E, Betts F, Sherman P, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of human osteonal bone. Calcif Tissue Int. 1996;59:480–487.PubMed
54.
Paschalis EP, Shane E, Lyritis G, Skarantavos G, Mendelsohn R, Boskey AL. Bone fragility and collagen cross-links. J Bone Miner Res. 2004;19:2000–2004.PubMedCrossRef
55.
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;16:1821–1828.PubMedCrossRef
56.
Pasteris JD, Wopenka B, Freeman JJ, Rogers K, Valsami-Jones E, van der Houwen JAM, Silva MJ. Lack of OH in nanocrystalline apatite as a function of degree of atomic order: implications for bone and biomaterials. Biomaterials. 2004;25:229–238.PubMedCrossRef
57.
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.PubMedCrossRef
58.
Penel G, Leroy G, Rey C, Bres E. MicroRaman spectral study of the PO4 and CO3 vibrational modes in synthetic and biological apatites. Calcif Tissue Int. 1998;63:475–481.PubMedCrossRef
59.
Pettway GJ, Schneider A, Koh AJ, Widjaja E, Morris MD, Meganck JA, Goldstein SA, McCauley LK. Anabolic actions of PTH (1-34): use of a novel tissue engineering model to investigate temporal effects on bone. Bone. 2005;36:959–970.PubMedCrossRef
60.
Pezzotti G. Raman piezo-spectroscopic analysis of natural and synthetic biomaterials. Anal Bioanal Chem. 2005;381:577–590.PubMedCrossRef
61.
Raghavan M, Sahar N, Wilson RH, Mycek M-A, Pleshko N, Kohn DH, Morris MD. Quantitative polarized Raman spectroscopy in highly turbid bone tissue. J Biomed Opt. 2010;15:037001.PubMedCrossRef
62.
Rohleder D, Kocherscheidt G, Gerber K, Kiefer W, Kohler W, Mocks J, Petrich W. Comparison of mid-infrared and Raman spectroscopy in the quantitative analysis of serum. J Biomed Opt. 2005;10:031108.PubMedCrossRef
63.
Schlucker S, Schaeberle MD, Huffman SW, Levin IW. Raman microspectroscopy: a comparison of point, line, and wide-field imaging methodologies. Anal Chem. 2003;75:4312–4318.PubMedCrossRef
64.
Schulmerich MV, Cole JH, Dooley KA, Morris MD, Kreider JM, Goldstein SA, Srinivasan S, Pogue BW. Noninvasive Raman tomographic imaging of canine bone tissue. J Biomed Opt. 2008;13:020506.PubMedCrossRef
65.
Schulmerich MV, Cole JH, Kreider JM, Esmonde-White F, Dooley KA, Goldstein SA, Morris MD. Transcutaneous Raman spectroscopy of murine bone in vivo. Appl Spectrosc. 2009;63:286–295.PubMedCrossRef
66.
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.PubMedCrossRef
67.
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;61:671–678.PubMedCrossRef
68.
Shea DA, Morris MD. Bone tissue fluorescence reduction for visible laser Raman spectroscopy. Applied Spectrosciot. 2002;56:182–186.CrossRef
69.
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;21:81–87.PubMedCrossRef
70.
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.PubMedCrossRef
71.
Silver FH, Kato YP, Ohno M, Wasserman AJ. Analysis of mammalian connective tissue: relationship between hierarchical structures and mechanical properties. J Long Term Eff Med Implants. 1992;2:165–198.PubMed
72.
Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner W, Nevitt MC, Cummings SR, Osteoporotic Fractures Research Group. BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res. 2003;18:1947–1954.PubMedCrossRef
73.
Tarnowski CP, Ignelzi MA, Morris MD. Mineralization of developing mouse calvaria as revealed by Raman microspectroscopy. J Bone Miner Res. 2002;17:1118–1126.PubMedCrossRef
74.
Tarnowski CP, Ignelzi MA, Wang W, Taboas JM, Goldstein SA, Morris MD. Earliest mineral and matrix changes in force-induced musculoskeletal disease as revealed by Raman microspectroscopic imaging. J Bone Miner Res. 2004;19:64–71.PubMedCrossRef
75.
Timlin JA, Carden A, Morris MD, Rajachar RM, Kohn DH. Raman spectroscopic imaging markers for fatigue-related microdamage in bovine bone. Anal Chem. 2000;72:2229–2236.PubMedCrossRef
76.
Uthgenannt BA, Kramer MH, Hwu JA, Wopenka B, Silva MJ. Skeletal self-repair: stress fracture healing by rapid formation and densification of woven bone. J Bone Miner Res. 2007;22:1548–1556.PubMedCrossRef
77.
Wallace JM, Golcuk K, Morris MD, Kohn DH. Inbred strain-specific effects of exercise in wild type and biglycan deficient mice. Ann Biomed Eng. 2010;38:1607–1617.PubMedCrossRef
78.
Wallace JM, Golcuk K, Morris MD, Kohn DH. Inbred strain-specific response to biglycan deficiency in the cortical bone of C57BL6/129 and C3H/He mice. J Bone Miner Res. 2009;24:1002–1012.PubMedCrossRef
79.
Wopenka B, Kent A, Pasteris JD, Yoon Y, Thomopoulos S. The tendon-to-bone transition of the rotator cuff: a preliminary Raman spectroscopic study documenting the gradual mineralization across the insertion in rat tissue samples. Appl Spectrosc. 2008;62:1285–1294.PubMedCrossRef
80.
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;78:363–371.PubMedCrossRef
81.
Yerramshetty JS, Akkus O. The associations between mineral crystallinity and the mechanical properties of human cortical bone. Bone. 2008;42:476–482.PubMedCrossRef
82.
Yerramshetty JS, Lind C, Akkus O. The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade. Bone. 2006;39:1236–1243.PubMedCrossRef
Metadata
Title
Raman Assessment of Bone Quality
Authors
Michael D. Morris, PhD
Gurjit S. Mandair, PhD
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 8/2011
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-010-1692-y

Other articles of this Issue 8/2011

Clinical Orthopaedics and Related Research® 8/2011 Go to the issue

Symposium: Bone Quality: From Bench to Bedside

High-resolution Computed Tomography for Clinical Imaging of Bone Microarchitecture

Clinical Research

Does Fresh Osteochondral Allograft Transplantation of Talar Osteochondral Defects Improve Function?

Letter to the Editor

Letter to the Editor: Bony Increased-offset Reversed Shoulder Arthroplasty: Minimizing Scapular Impingement While Maximizing Glenoid Fixation

Symposium: UHMWPE for Arthroplasty: From Powder to Debris

Do Tissues From THA Revision of Highly Crosslinked UHMWPE Liners Contain Wear Debris and Associated Inflammation?

Reply to Letter to the Editor

Reply to Letter to the Editor: Bony Increased-offset Reversed Shoulder Arthroplasty: Minimizing Scapular Impingement While Maximizing Glenoid Fixation

Symposium: Bone Quality: From Bench to Bedside

Bone Quality: Educational Tools for Patients, Physicians, and Educators