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Clinical Orthopaedics and Related Research®

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

Methods for Assessing Bone Quality: A Review

Author: Eve Donnelly, PhD

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

Abstract

Background

Bone mass, geometry, and tissue material properties contribute to bone structural integrity. Thus, bone strength arises from both bone quantity and quality. Bone quality encompasses the geometric and material factors that contribute to fracture resistance.

Questions/purposes

This review presents an overview of the methods for assessing bone quality across multiple length scales, their outcomes, and their relative advantages and disadvantages.

Methods

A PubMed search was conducted to identify methods related to bone mechanical testing, imaging, and compositional analysis. Using various exclusion criteria, articles were selected for inclusion.

Results

Methods for assessing mechanical properties include whole-bone, bulk tissue, microbeam, and micro- and nanoindentation testing techniques. Outcomes include structural strength and material modulus. Advantages include direct assessment of bone strength; disadvantages include specimen destruction during testing. Methods for characterizing bone geometry and microarchitecture include quantitative CT, high-resolution peripheral quantitative CT, high-resolution MRI, and micro-CT. Outcomes include three-dimensional whole-bone geometry, trabecular morphology, and tissue mineral density. The primary advantage is the ability to image noninvasively; disadvantages include the lack of a direct measure of bone strength. Methods for measuring tissue composition include scanning electron microscopy, vibrational spectroscopy, nuclear magnetic resonance imaging, and chemical and physical analytical techniques. Outcomes include mineral density and crystallinity, elemental composition, and collagen crosslink composition. Advantages include the detailed material characterization; disadvantages include the need for a biopsy.

Conclusions

Although no single method can completely characterize bone quality, current noninvasive imaging techniques can be combined with ex vivo mechanical and compositional techniques to provide a comprehensive understanding of bone quality.

Anumula S, Magland J, Wehrli SL, Zhang H, Ong H, Song HK, Wehrli FW. Measurement of phosphorus content in normal and osteomalacic rabbit bone by solid-state 3D radial imaging. Magn Reson Med. 2006;56:946–952.PubMedCrossRef

Avery NC, Sims TJ, Bailey AJ. Quantitative determination of collagen cross-links. Methods Mol Biol. 2009;522:103–121.PubMedCrossRef

Bailey AJ, Sims TJ, Ebbesen EN, Mansell JP, Thomsen JS, Mosekilde L. Age-related changes in the biochemical properties of human cancellous bone collagen: relationship to bone strength. Calcif Tissue Int. 1999;65:203–210.PubMedCrossRef

Bauer JS, Link TM. Advances in osteoporosis imaging. Eur J Radiol. 2009;71:440–449.PubMedCrossRef

Bloebaum RD, Skedros JG, Vajda EG, Bachus KN, Constantz BR. Determining mineral content variations in bone using backscattered electron imaging. Bone. 1997;20:485–490.PubMedCrossRef

Boskey A. Bone mineralization. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:5.1–5.33.

Boskey A, Mendelsohn R. Infrared analysis of bone in health and disease. J Biomed Opt. 2005;10:031102.PubMedCrossRef

Boskey A, Pleshko Camacho N. FT-IR imaging of native and tissue-engineered bone and cartilage. Biomaterials. 2007;28:2465–2478.PubMedCrossRef

Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005;90:6508–6515.PubMedCrossRef

10.

Bouxsein ML. Bone quality: where do we go from here? Osteoporos Int. 2003;14(Suppl 5):S118–S127.PubMedCrossRef

11.

Boyde A. Scanning electron microscope studies of bone. In: Bourne GH, ed. The Biochemistry and Physiology of Bone. 2nd ed. New York, NY: Academic Press; 1972:259–310.

12.

Brodt MD, Ellis CB, Silva MJ. Growing C57Bl/6 mice increase whole bone mechanical properties by increasing geometric and material properties. J Bone Miner Res. 1999;14:2159–2166.PubMedCrossRef

13.

Brown CE, Battocletti JH, Srinivasan R, Allaway JR, Moore J, Sigmann P. In vivo 31P nuclear magnetic resonance spectroscopy of bone mineral for evaluation of osteoporosis. Clin Chem. 1988;34:1431–1438.PubMed

14.

Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S. A longitudinal HR-pQCT study of alendronate treatment in post-menopausal women with low bone density: relations between density, cortical and trabecular micro-architecture, biomechanics, and bone turnover. J Bone Miner Res. 2010 June 18 [Epub ahead of print].

15.

Burstein AH, Zika JM, Heiple KG, Klein L. Contribution of collagen and mineral to the elastic-plastic properties of bone. J Bone Joint Surg Am. 1975;57:956–961.PubMed

16.

Camacho NP, Hou L, Toledano TR, Ilg WA, Brayton CF, Raggio CL, Root L, Boskey AL. The material basis for reduced mechanical properties in oim mice bones. J Bone Miner Res. 1999;14:264–272.PubMedCrossRef

17.

Carballido-Gamio J, Majumdar S. Clinical utility of microarchitecture measurements of trabecular bone. Curr Osteoporos Rep. 2006;4:64–70.PubMedCrossRef

18.

Carden A, Morris MD. Application of vibrational spectroscopy to the study of mineralized tissues (review). J Biomed Opt. 2000;5:259–268.PubMedCrossRef

19.

Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg Am. 1977;59:954–962.PubMed

20.

Choi K, Kuhn JL, Ciarelli MJ, Goldstein SA. The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus. J Biomech. 1990;23:1103–1113.PubMedCrossRef

21.

Chung HW, Wehrli FW, Williams JL, Kugelmass SD, Wehrli SL. Quantitative analysis of trabecular microstructure by 400 MHz nuclear magnetic resonance imaging. J Bone Miner Res. 1995;10:803–811.PubMedCrossRef

22.

Code RF, Harrison JE, McNeill KG. In vivo measurement of accumulated bone fluorides by nuclear magnetic resonance. J Bone Miner Res. 1990;5(Suppl 1):S91–S94.PubMed

23.

Crawford RP, Cann CE, Keaveny TM. Finite element models predict in vitro vertebral body compressive strength better than quantitative computed tomography. Bone. 2003;33:744–750.PubMedCrossRef

24.

Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. 2002;288:1889–1897.PubMedCrossRef

25.

Currey JD. The mechanical consequences of variation in the mineral content of bone. J Biomech. 1969;2:1–11.PubMedCrossRef

26.

Currey JD. The relationship between the stiffness and the mineral content of bone. J Biomech. 1969;2:477–480.PubMedCrossRef

27.

Currey JD. The effect of porosity and mineral content on the Young’s modulus of elasticity of compact bone. J Biomech. 1988;21:131–139.PubMedCrossRef

28.

Donnelly E, Baker SP, Boskey AL, van der Meulen MC. Effects of surface roughness and maximum load on the mechanical properties of cancellous bone measured by nanoindentation. J Biomed Mater Res A. 2006;77:426–435.PubMed

29.

Donnelly E, Williams RM, Downs SA, Dickinson ME, Baker SP, van der Meulen MC. Quasistatic and dynamic nanomechanical properties of cancellous bone tissue relate to collagen content and organization. J Mater Res. 2006;21:2106–2117.CrossRef

30.

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;20:1968–1972.PubMedCrossRef

31.

Fernandez-Seara MA, Wehrli SL, Takahashi M, Wehrli FW. Water content measured by proton-deuteron exchange NMR predicts bone mineral density and mechanical properties. J Bone Miner Res. 2004;19:289–296.PubMedCrossRef

32.

Genant HK, Engelke K, Prevrhal S. Advanced CT bone imaging in osteoporosis. Rheumatology (Oxford). 2008;47(Suppl 4): iv9–iv16.

33.

Goldstein SA, Wilson DL, Sonstegard DA, Matthews LS. The mechanical properties of human tibial trabecular bone as a function of metaphyseal location. J Biomech. 1983;16:965–969.PubMedCrossRef

34.

Gordon CL, Lang TF, Augat P, Genant HK. Image-based assessment of spinal trabecular bone structure from high-resolution CT images. Osteoporos Int. 1998;8:317–325.PubMedCrossRef

35.

Gourion-Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, Shane E, Recker RR, Boskey ER, Boskey AL. Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res. 2009;24:1565–1571.PubMedCrossRef

36.

Hansma P, Turner P, Drake B, Yurtsev E, Proctor A, Mathews P, Lulejian J, Randall C, Adams J, Jungmann R, Garza-de-Leon F, Fantner G, Mkrtchyan H, Pontin M, Weaver A, Brown MB, Sahar N, Rossello R, Kohn D. The bone diagnostic instrument II: indentation distance increase. Rev Sci Instrum. 2008;79:064303.PubMedCrossRef

37.

Hengsberger S, Enstroem J, Peyrin F, Zysset P. How is the indentation modulus of bone tissue related to its macroscopic elastic response? A validation study. J Biomech. 2003;36:1503–1509.PubMedCrossRef

38.

Hengsberger S, Kulik A, Zysset P. Nanoindentation discriminates the elastic properties of individual human bone lamellae under dry and physiological conditions. Bone. 2002;30:178–184.PubMedCrossRef

39.

Howell PG, Boyde A. Monte Carlo simulations of electron scattering in bone. Bone. 1994;15:285–291.PubMedCrossRef

40.

Howell PG, Boyde A. Volumes from which calcium and phosphorus X-rays arise in electron probe emission microanalysis of bone: Monte Carlo simulation. Calcif Tissue Int. 2003;72:745–749.PubMedCrossRef

41.

Judex S, Boyd S, Qin YX, Miller L, Muller 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

42.

Kazakia GJ, Burghardt AJ, Cheung S, Majumdar S. Assessment of bone tissue mineralization by conventional x-ray microcomputed tomography: comparison with synchrotron radiation microcomputed tomography and ash measurements. Med Phys. 2008;35:3170–3179.PubMedCrossRef

43.

Kazakia GJ, Majumdar S. New imaging technologies in the diagnosis of osteoporosis. Rev Endocr Metab Disord. 2006;7:67–74.PubMedCrossRef

44.

Keaveny TM. Biomechanical computed tomography-noninvasive bone strength analysis using clinical computed tomography scans. Ann N Y Acad Sci. 2010;1192:57–65.PubMedCrossRef

45.

Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA. Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis. J Bone Miner Res. 2007;22:149–157.PubMedCrossRef

46.

Keaveny TM, Wachtel EF, Ford CM, Hayes WC. Differences between the tensile and compressive strengths of bovine tibial trabecular bone depend on modulus. J Biomech. 1994;27:1137–1146.PubMedCrossRef

47.

Kuhn JL, Goldstein SA, Choi K, London M, Feldkamp LA, Matthews LS. Comparison of the trabecular and cortical tissue moduli from human iliac crests. J Orthop Res. 1989;7:876–884.PubMedCrossRef

48.

Kuhn LT, Grynpas MD, Rey CC, Wu Y, Ackerman JL, Glimcher MJ. A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages. Calcif Tissue Int. 2008;83:146–154.PubMedCrossRef

49.

Lambert JB, Simpson SV, Buikstra JE, Hanson D. Electron microprobe analysis of elemental distribution in excavated human femurs. Am J Phys Anthropol. 1983;62:409–423.PubMedCrossRef

50.

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

51.

Lang TF, Leblanc AD, Evans HJ, Lu Y. Adaptation of the proximal femur to skeletal reloading after long-duration spaceflight. J Bone Miner Res. 2006;21:1224–1230.PubMedCrossRef

52.

Link TM. Correlations between joint morphology and pain and between magnetic resonance imaging, histology, and micro-computed tomography. J Bone Joint Surg Am. 2009;91(Suppl 1):30–32.PubMedCrossRef

53.

Link TM, Majumdar S. Current diagnostic techniques in the evaluation of bone architecture. Curr Osteoporos Rep. 2004;2:47–52.PubMedCrossRef

54.

Liu-Ambrose TY, Khan KM, Eng JJ, Heinonen A, McKay HA. Both resistance and agility training increase cortical bone density in 75- to 85-year-old women with low bone mass: a 6-month randomized controlled trial. J Clin Densitom. 2004;7:390–398.PubMedCrossRef

55.

MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. 2007;29:1096–1105.PubMedCrossRef

56.

Majumdar S, Genant HK, Grampp S, Newitt DC, Truong VH, Lin JC, Mathur A. Correlation of trabecular bone structure with age, bone mineral density, and osteoporotic status: in vivo studies of the distal radius using high resolution magnetic resonance imaging. J Bone Miner Res. 1997;12:111–118.PubMedCrossRef

57.

Majumdar S, Kothari M, Augat P, Newitt DC, Link TM, Lin JC, Lang T, Lu Y, Genant HK. High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties. Bone. 1998;22:445–454.PubMedCrossRef

58.

Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:1254–1259.PubMed

59.

Moore JR, Garrido L, Ackerman JL. Solid state phosphorus-31 magnetic resonance imaging of bone mineral. Magn Reson Med. 1995;33:293–299.PubMedCrossRef

60.

Morgan EF, Keaveny TM. Dependence of yield strain of human trabecular bone on anatomic site. J Biomech. 2001;34:569–577.PubMedCrossRef

61.

Morgan EF, Mason ZD, Chien KB, Pfeiffer AJ, Barnes GL, Einhorn TA, Gerstenfeld LC. Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function. Bone. 2009;44:335–344.PubMedCrossRef

62.

Muller R, van Lenthe GH. Trabecular bone failure at the microstructural level. Curr Osteoporos Rep. 2006;4:80–86.PubMedCrossRef

63.

Nyman JS, Ni Q, Nicolella DP, Wang X. Measurements of mobile and bound water by nuclear magnetic resonance correlate with mechanical properties of bone. Bone. 2008;42:193–199.PubMedCrossRef

64.

Oliver WC, Pharr GM. Improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res. 1992;7:1564–1583.CrossRef

65.

Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987;2:595–610.PubMedCrossRef

66.

Peyrin F, Salome M, Cloetens P, Laval-Jeantet AM, Ritman E, Ruegsegger P. Micro-CT examinations of trabecular bone samples at different resolutions: 14, 7 and 2 micron level. Technol Health Care. 1998;6:391–401.PubMed

67.

Pistoia W, van Rietbergen B, Laib A, Ruegsegger P. High-resolution three-dimensional-pQCT images can be an adequate basis for in-vivo microFE analysis of bone. J Biomech Eng. 2001;123:176–183.PubMedCrossRef

68.

Reilly DT, Burstein AH. The elastic and ultimate properties of compact bone tissue. J Biomech. 1975;8:393–405.PubMedCrossRef

69.

Rho JY, Roy ME 2nd, Tsui TY, Pharr GM. Elastic properties of microstructural components of human bone tissue as measured by nanoindentation. J Biomed Mater Res. 1999;45:48–54.PubMedCrossRef

70.

Roschger P, Fratzl-Zelman N, Misof BM, Glorieux FH, Klaushofer K, Rauch F. Evidence that abnormal high bone mineralization in growing children with osteogenesis imperfecta is not associated with specific collagen mutations. Calcif Tissue Int. 2008;82:263–270.PubMedCrossRef

71.

Roschger P, Manjubala I, Zoeger N, Meirer F, Simon R, Li C, Fratzl-Zelman N, Misof B, Paschalis E, Streli C, Fratzl P, Klaushofer K. 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.PubMedCrossRef

72.

Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. 2008;42:456–466.PubMedCrossRef

73.

Ruegsegger P, Koller B, Muller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int. 1996;58:24–29.PubMedCrossRef

74.

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

75.

Sell DR, Monnier VM. Isolation, purification and partial characterization of novel fluorophores from aging human insoluble collagen-rich tissue. Connect Tissue Res. 1989;19:77–92.PubMedCrossRef

76.

Tang SY, Zeenath U, Vashishth D. Effects of non-enzymatic glycation on cancellous bone fragility. Bone. 2007;40:1144–1151.PubMedCrossRef

77.

Techawiboonwong A, Song HK, Leonard MB, Wehrli FW. Cortical bone water: in vivo quantification with ultrashort echo-time MR imaging. Radiology. 2008;248:824–833.PubMedCrossRef

78.

Tseng KF, Bonadio JF, Stewart TA, Baker AR, Goldstein SA. Local expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice. J Orthop Res. 1996;14:598–604.PubMedCrossRef

79.

Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone. 1993;14:595–608.PubMedCrossRef

80.

van der Meulen MC, Jepsen KJ, Mikic B. Understanding bone strength: size isn’t everything. Bone. 2001;29:101–104.PubMedCrossRef

81.

Vashishth D. The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep. 2007;5:62–66.PubMedCrossRef

82.

Voide R, Schneider P, Stauber M, Wyss P, Stampanoni M, Sennhauser U, van Lenthe GH, Muller R. Time-lapsed assessment of microcrack initiation and propagation in murine cortical bone at submicrometer resolution. Bone. 2009;45:164–173.PubMedCrossRef

83.

Waarsing JH, Day JS, van der Linden JC, Ederveen AG, Spanjers C, De Clerck N, Sasov A, Verhaar JA, Weinans H. Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data. Bone. 2004;34:163–169.PubMedCrossRef

84.

Wehrli FW, Fernandez-Seara MA. Nuclear magnetic resonance studies of bone water. Ann Biomed Eng. 2005;33:79–86.PubMedCrossRef

85.

Wu Y, Ackerman JL, Chesler DA, Li J, Neer RM, Wang J, Glimcher MJ. Evaluation of bone mineral density using three-dimensional solid state phosphorus-31 NMR projection imaging. Calcif Tissue Int. 1998;62:512–518.PubMedCrossRef

86.

Wu Y, Chesler DA, Glimcher MJ, Garrido L, Wang J, Jiang HJ, Ackerman JL. Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates. Proc Natl Acad Sci USA. 1999;96:1574–1578.PubMedCrossRef

87.

Wu Y, Hrovat MI, Ackerman JL, Reese TG, Cao H, Ecklund K, Glimcher MJ. Bone matrix imaged in vivo by water- and fat-suppressed proton projection MRI (WASPI) of animal and human subjects. J Magn Reson Imaging. 2010;31:954–963.PubMedCrossRef

88.

Ziv V, Wagner HD, Weiner S. Microstructure-microhardness relations in parallel-fibered and lamellar bone. Bone. 1996;18:417–428.PubMedCrossRef

89.

Zysset PK. Indentation of bone tissue: a short review. Osteoporos Int. 2009;20:1049–1055.PubMedCrossRef

Title: Methods for Assessing Bone Quality: A Review
Author: Eve Donnelly, 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/s11999-010-1702-0

At a glance: The STEP trials

Springer Medicine

Methods for Assessing Bone Quality: A Review

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

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