Bone volume fraction explains the variation in strength and stiffness of cancellous bone affected by metastatic cancer and osteoporosis

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Nazarian, Ara^1,2; von Stechow, Dietrich¹; Zurakowski, David³; Müller, Ralph⁴; Snyder, Brian D.^1,3

Bone volume fraction explains the variation in strength and stiffness of cancellous bone affected by metastatic cancer and osteoporosis

Calcif Tiss Int. December 2008;83(6):368-379

©2008 Springer Science+Business Media, LLC

Affiliations

¹Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

²Institute for Biomedical Engineering, University and ETH Zürich, Zürich 8044, Switzerland

³Department of Orthopedic Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA

⁴Institute for Biomechanics, ETH Zürich, Zürich 8044, Switzerland
Abstract and keywords

Preventing nontraumatic fractures in millions of patients with osteoporosis or metastatic cancer may significantly reduce the associated morbidity and reduce health-care expenditures incurred by these fractures. Predicting fracture occurrence requires an accurate understanding of the relationship between bone structure and the mechanical properties governing bone fracture that can be readily measured. The aim of this study was to test the hypothesis that a single analytic relationship with either bone tissue mineral density or bone volume fraction (BV/TV) as independent variables could predict the strength and stiffness of normal and pathologic cancellous bone affected by osteoporosis or metastatic cancer. After obtaining institutional review board approval and informed consent, 15 patients underwent excisional biopsy of metastatic prostate, breast, lung, ovarian, or colon cancer from the spine and/or femur to obtain 41 metastatic cancer specimens. In addition, 96 noncancer specimens were excised from 43 age- and site-matched cadavers. All specimens were imaged using micro-computed tomography (micro-CT) and backscatter emission imaging and tested mechanically by uniaxial compression and nanoindentation. The minimum BV/TV, measured using quantitative micro-CT, accounted for 84% of the variation in bone stiffness and strength for all cancellous bone specimens. While relationships relating bone density to strength and stiffness have been derived empirically for normal and osteoporotic bone, these relationships have not been applied to skeletal metastases. This simple analytic relationship will facilitate large-scale screening and prediction of fracture risk for normal and pathologic cancellous bone using clinical CT systems to determine the load capacity of bones altered by metastatic cancer, osteoporosis, or both.

Keywords: Osteoporosis; Skeletal metastasis; Cancellous bone; Mechanical property; Bone volume fraction; Bone mineral density
Links

DOI: 10.1007/s00223-008-9174-x

PubMed: 18946628

WoS: 000261374600002
History

Received: 2008-06-05

Accepted: 2008-08-25

Online: 2008-10-23

Cited Works (59)

Year	Entry
1993	Snyder BD, Piazza S, Edwards WT, Hayes WC. Role of trabecular morphology in the etiology of age-related vertebral fractures. Calcif Tiss Int. February 1993;53(suppl 1):S14-S22.
1988	Schaffler MB, Burr DB. Stiffness of compact bone: effects of porosity and density. J Biomech. 1988;21(1):13-16.
1996	Rüegsegger P, Koller B, Müller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tiss Int. 1996;58(1):24-29.
1997	Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191-199.
2000	Whealan KM, Kwak SD, Tedrow JR, Inoue K, Snyder BD. Noninvasive imaging predicts failure load of the spine with simulated osteolytic defects. J Bone Joint Surg. September 2000;82A(9):1240-1251.
2001	Hernandez CJ, Beaupré GS, Keller TS, Carter DR. The influence of bone volume fraction and ash fraction on bone strength and modulus. Bone. July 2001;29(1):74-78.
1993	Keaveny TM, Borchers RE, Gibson LJ, Hayes WC. Theoretical analysis of the experimental artifact in trabecular bone compressive modulus [published correction appears in J Biomech. 1993;26(9):1143]. J Biomech. April–May 1993;26(4-5):599-607.
2003	Kowalczyk P. Elastic properties of cancellous bone derived from finite element models of parameterized microstructure cells. J Biomech. July 2003;36(7):961-972.
1999	Kabel J, van Rietbergen B, Odgaard A, Huiskes R. Constitutive relationships of fabric, density, and elastic properties in cancellous bone architecture. Bone. October 1999;25(4):481-486.
1997	Keaveny TM, Pinilla TP, Crawford RP, Kopperdahl DL, Lou A. Systematic and random errors in compression testing of trabecular bone [published correction appears in J Orthop Res. 1995;17(1):151]. J Orthop Res. 1997;15(1):101-110.
1994	Goulet RW, Goldstein SA, Ciarelli MJ, Kuhn JL, Brown MB, Feldkamp LA. The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech. April 1994;27(4):375-389.
1996	Ford CM, Keaveny TM. The dependence of shear failure properties of trabecular bone on apparent density and trabecular orientation. J Biomech. 1996;29(10):1309-1317.
2002	Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int. February 2002;13(2):97-104.
2004	Hong J, Cabe GD, Tedrow JR, Hipp JA, Snyder BD. Failure of trabecular bone with simulated lytic defects can be predicted non-invasively by structural analysis. J Orthop Res. May 2004;22(3):479-486.
2005	Nazarian A, Stauber M, Müller R. Design and implementation of a novel mechanical testing system for cellular solids. J Biomed Mater Res. 2005;B73(2):400-411.
2007	Kim D-G, Hunt CA, Zauel R, Fyhrie DP, Yeni YN. The effect of regional variations of the trabecular bone properties on the compressive strength of human vertebral bodies. Ann Biomed Eng. November 2007;35(11):1907-1913.
2004	Yeni YN, Dong XN, Fyhrie DP, Les CM. The dependence between the strength and stiffness of cancellous and cortical bone tissue for tension and compression: extension of a unifying principle. Bio-med Mater Eng. 2004;14(3):303-310.
2005	Keyak JH, Kaneko TS, Tehranzadeh J, Skinner HB. Predicting proximal femoral strength using structural engineering models. Clin Orthop Relat Res. August 2005;437:219-228.
2004	Nazarian A, Müller R. Time-lapsed microstructural imaging of bone failure behavior. J Biomech. 2004;37(1):55-65.
1976	Carter DR, Hayes WC. Bone compressive strength: the influence of density and strain rate. Science. September 10, 1976;194(4270):1174-1176.
1994	Keller TS. Predicting the compressive mechanical behavior of bone. J Biomech. September 1994;27(9):1159-1168.
1990	Hodgskinson R, Currey JD. The effect of variation in structure on the Young's modulus of cancellous bone: a comparison of human and non-human material. Proc Inst Mech Eng Part H-J Eng Med. 1990;204(2):115-121.
1993	Michel MC, Guo X-DE, Gibson LJ, McMahon TA, Hayes WC. Compressive fatigue behavior of bovine trabecular bone. J Biomech. April–May 1993;26(4-5):453-463.
2003	Kaneko TS, Pejcic MR, Tehranzadeh J, Keyak JH. Relationships between material properties and CT scan data of cortical bone with and without metastatic lesions. Med Eng Phys. July 2003;25(6):445-454.
2002	Newitt DC, Majumdar S, van Rietbergen B, von Ingersleben G, Harris ST, Genant HK, Chesnut C, Garnero P, MacDonald B. In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius. Osteoporos Int. January 2002;13(1):6-17.
1993	Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palmero L, Scott J, Vogt TM; Study of Osteoporotic Fractures Research Group. Bone density at various sites for prediction of hip fractures. Lancet. January 9, 1993;341(8837):72-75.
1994	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(9):1137-1146.
1999	Keaveny TM, Wachtel EF, Zadesky SP, Arramon YP. Application of the Tsai–Wu quadratic multiaxial failure criterion to bovine trabecular bone. J Biomech Eng. February 1999;121(1):99-107.
1988	Rice JC, Cowin SC, Bowman JA. On the dependence of the elasticity and strength of cancellous bone on apparent density. J Biomech. 1988;21(2):155-168.
1985	McBroom RJ, Hayes WC, Edwards WT, Goldberg RP, White AA III. Prediction of vertebral body compressive fracture using quantitative computed tomography. J Bone Joint Surg. 1985;67A(8):1206-1214.
1997	Gibson LJ, Ashby MF. Cellular Solids: Structure and Properties. 2nd ed. Cambridge, UK: Cambridge University Press; 1997. Cambridge Solid State Science Series.
1987	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. December 1987;2(6):595-610.
1986	Riggs BL, Melton LJ III. Involutional osteoporosis. NEJM. June 26, 1986;314(26):1676-1686.
1992	Oliver WC, Pharr GM. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res. 1992;7(6):1564-1583.
2005	Gibson LJ. Biomechanics of cellular solids. J Biomech. 2005;38(3):377-399.
1990	Turner CH, Cowin SC, Rho JY, Ashman RB, Rice JC. The fabric dependence of the orthotropic elastic constants of cancellous bone. J Biomech. 1990;23(6):549-561.
2002	Wehrli F, Saha P, Gomberg B, Song H, Snyder P, Benito M, Wright A, Weening R. Role of magnetic resonance for assessing structure and function of trabecular bone. Top Magn Reson Imaging. October 2002;13(5):335-355.
2005	Diab T, Vashishth D. Effects of damage morphology on cortical bone fragility. Bone. July 2005;37(1):96-102.
1970	Timoshenko SP, Goodier JN. Theory of Elasticity. 3rd ed. New York, NY: McGraw-Hill Book Co; 1970.
2004	Kaneko TS, Bell JS, Pejcic MR, Tehranzadeh J, Keyak JH. Mechanical properties, density and quantitative CT scan data of trabecular bone with and without metastases. J Biomech. April 2004;37(4):523-530.
1997	Yeni YN, Brown CU, Wang Z, Norman TL. The influence of bone morphology on fracture toughness of the human femur and tibia. Bone. November 1997;21(4):453-459.
1984	Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. February 13, 1984;304(1121):509-518.
2006	Bevill G, Eswaran SK, Gupta A, Papadopoulos P, Keaveny TM. Influence of bone volume fraction and architecture on computed large-deformation failure mechanisms in human trabecular bone. Bone. December 2006;39(6):1218-1225.
1999	Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P. Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. July 1999;14(7):1167-1174.
1998	Müller R, Gerber SC, Hayes WC. Micro-compression: a novel technique for the nondestructive assessment of local bone failure. Technol Health Care. December 1998;6(5-6):433-444.
2003	Crawford RP, Cann CE, Keaveny TM. Finite element models predict in vitro vertebral body compressive strength better than quantitative computed tomography. Bone. 2003;33(4):744-750.
1987	Lorensen WE, Cline HE. Marching cubes: a high resolution 3D surface construction algorithm. Comput Graph. 1987;21(4):163-169.
2005	Mayhew PM, Thomas CD, Clement JG, Loveridge N, Beck TJ, Bonfield W, Burgoyne CJ, Reeve J. Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet. July 9, 2005;366(9480):129-135.
1997	Silva MJ, Keaveny TM, Hayes WC. Load sharing between the shell and centrum in the lumbar vertebral body. Spine. January 1997;22(2):140-150.
1998	Hou FJ, Lang SM, Hoshaw SJ, Reimann DA, Fyhrie DP. Human vertebral body apparent and hard tissue stiffness. J Biomech. November 1998;31(11):1009-1015.
1977	Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59A(7):954-962.
1991	Cody DD, Goldstein SA, Flynn MJ, Brown EB. Correlations between vertebral regional bone mineral density (rBMD) and whole bone fracture load. Spine. 1991;16(2):146-154.
1999	Zioupos P, Currey JD, Hamer AJ. The role of collagen in the declining mechanical properties of aging human cortical bone. J Biomed Mater Res. May 1999;A45(2):108-116.
1998	Van Rietbergen B, Odgaard A, Kabel J, Huiskes R. Relationships between bone morphology and bone elastic properties can be accurately quantified using high‐resolution computer reconstructions. J Orthop Res. January 1998;16(1):23-28.
1985	Cowin SC. The relationship between the elasticity tensor and the fabric tensor. Mech Mater. 1985;4(2):137-147.
2004	Bourne BC, van der Meulen MCH. Finite element models predict cancellous apparent modulus when tissue modulus is scaled from specimen CT-attenuation. J Biomech. May 2004;37(5):613-621.
2006	Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength. Osteoporos Int. March 2006;17(3):319-336.
2003	Homminga J, McCreadie BR, Weinans H, Huiskes R. The dependence of the elastic properties of osteoporotic cancellous bone on volume fraction and fabric. J Biomech. October 2003;36(10):1461-1467.
1993	Keaveny TM, Borchers RE, Gibson L, Hayes WC. Trabecular bone modulus and strength can depend on specimen geometry. J Biomech. August 1993;26(8):991-995.

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2019	Sohail A, Younas M, Bhatti Y, Li Z, Tunç S, Abid M. Analysis of trabecular bone mechanics using machine learning. Evol Bioinform. March 24, 2019;15:1176934318825084.
2012	Nikodem A. Correlations between structural and mechanical properties of human trabecular femur bone. Acta Bioeng Biomech. 2012;14(2):37-46.
2011	Öhman C, Baleani M, Pani C, Taddei F, Alberghini M, Viceconti M, Manfrini M. Compressive behaviour of child and adult cortical bone. Bone. October 2011;49(4):769-776.
2013	Hambli R. Micro-CT finite element model and experimental validation of trabecular bone damage and fracture. Bone. October 2013;56(2):363-374.
2020	Bailey S, Hackney D, Vashishth D, Alkalay RN. The effects of metastatic lesion on the structural determinants of bone: current clinical and experimental approaches. Bone. September 2020;138:115159.
2020	Stadelmann MA, Schenk DE, Maquer G, Lenherr C, Buck FM, Bosshardt DD, Hoppe S, Theumann N, Alkalay RN, Zysset PK. Conventional finite element models estimate the strength of metastatic human vertebrae despite alterations of the bone's tissue and structure. Bone. December 2020;141:115598.
2023	Palanca M, Cavazzoni G, Dall'Ara E. The role of bone metastases on the mechanical competence of human vertebrae. Bone. August 2023;173:116814.
2018	Zhao S, Arnold M, Ma S, Abel RL, Cobb JP, Hansen U, Boughton O. Standardizing compression testing for measuring the stiffness of human bone. Bone Joint Res. August 2018;7(8):524-538.
2023	Clausing RJ, Stiller A, Kuhn F, Fonseca Ulloa CA, Fölsch C, Kampschulte M, Krombach GA, Rickert M, Jahnke A. Measuring Young's modulus of single trabeculae in cancellous bone using a two-point bending test. Clin Biomech (Bristol, Avon). February 2023;102:105875.
2020	Whyne CM, Ferguson D, Clement A, Rangrez M, Hardisty M. Biomechanical properties of metastatically involved osteolytic bone. Curr Osteoporos Rep. December 2020;18(6):705-715.
2010	Tassani S, Öhman C, Baleani M, Baruffaldi F, Viceconti M. Anisotropy and inhomogeneity of the trabecular structure can describe the mechanical strength of osteoarthritic cancellous bone. J Biomech. April 19, 2010;43(6):1160-1166.
2011	Brynk T, Hellmich C, Fritsch A, Zysset P, Eberhardsteiner J. Experimental poromechanics of trabecular bone strength: role of Terzaghi's effective stress and of tissue level stress fluctuations. J Biomech. 2011;44(3):501-508.
2011	Nazarian A, Arroyo FJA, Rosso C, Aran S, Snyder BD. Tensile properties of rat femoral bone as functions of bone volume fraction, apparent density and volumetric bone mineral density. J Biomech. September 2, 2011;44(13):2482-2488.
2012	Tassani S, Matsopoulos GK, Baruffaldi F. 3D identification of trabecular bone fracture zone using an automatic image registration scheme: a validation study. J Biomech. July 26, 2012;45(11):2035-2040.
2014	Chen Y, Pani M, Taddei F, Mazzà C, Li X, Viceconti M. Large-scale finite element analysis of human cancellous bone tissue micro computer tomography data: a convergence study. J Biomech Eng. October 2014;136(10):101013.
2022	Bailey S, Stadelmann MA, Zysset PK, Vashishth D, Alkalay RN. Influence of metastatic bone lesion type and tumor origin on human vertebral bone architecture, matrix quality, and mechanical properties. J Bone Miner Res. May 2022;37(5):896-907.
2019	Molino G, Dalpozzi A, Ciapetti G, Lorusso M, Novara C, Cavallo M, Baldini N, Giorgis F, Fiorilli S, Vitale-Brovarone C. Osteoporosis-related variations of trabecular bone properties of proximal human humeral heads at different scale lengths. J Mech Behav Biomed Mater. December 2019;100:103373.
2020	Acciaioli A, Falco L, Balean M. Measurement of apparent mechanical properties of trabecular bone tissue: accuracy and limitation of digital image correlation technique. J Mech Behav Biomed Mater. March 2020;103:103542.
2022	Kusins J, Knowles N, Martensson N, Columbus MP, Athwal GS, Ferreira LM. Full-field experimental analysis of the influence of microstructural parameters on the mechanical properties of humeral head trabecular bone. J Orthop Res. September 2022;40(9):2048-2056.
2019	Mondal A, Nguyen C, Ma X, Elbanna AE, Carlson JM. Network models for characterization of trabecular bone. Phys Rev E. April 18, 2019;99(4):042406.
2017	Costa MC, Tozzi G, Cristofolini L, Danesi V, Viceconti M, Dall’Ara E. Micro finite element models of the vertebral body: validation of local displacement predictions. PLoS One. July 11, 2017;12(7):e0180151.
2019	Yeh P-S, Lee Y-W, Chang W-H, Wang W, Wang J-L, Liu S-H, Chen R-M. Biomechanical and tomographic differences in the microarchitecture and strength of trabecular and cortical bone in the early stage of male osteoporosis. PLoS One. 2019;14(8):e0219718.
2020	Smith SM, Angielczyk KD. Deciphering an extreme morphology: bone microarchitecture of the hero shrew backbone (Soricidae: Scutisorex). Proc R Soc B. May 13, 2020;287(1926):20200457.
2011	Cotter MM. Gross Morphology, Microarchitecture, Strength and Evolution of the Hominoid Vertebral Body [PhD thesis]. Cleveland, OH: Case Western Reserve University; May 2011.
2013	Kim G. The Effects of Mineralization and Crystallinity on the Mechanical Behavior of Bone [PhD thesis]. Ithaca, NY: Cornell University; May 2013.
2021	Sacher S. Characterization of Trabecular Morphology, Microdamage Accumulation, and Collagen Crosslinking in Bone Tissue from Individuals With Type II Diabetes Mellitus [Master's thesis]. Ithaca, NY: Cornell University; May 2021.
2019	Tourolle D. A Micro-Scale Multiphysics Framework for Fracture Healing and Bone Remodelling [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2019.
2014	Holub O. Biomechanics of Spinal Metastases [PhD thesis]. University of Leeds; April 2014.
2023	Young LAM. Analysis of Bone Structure in Peromyscus: Effects of Burrowing Behavior [Master's thesis]. Northeastern University; May 2023.
2011	Wu Z. Measures of Bone Quality and Their Relationship to Bone Mechanical Properties [PhD thesis]. University of Notre Dame; December 2011.
2011	Ahmed F. Multiscale Quantitative Imaging of Human Femoral Heads Using X-Ray Microtomography [PhD thesis]. Queen Mary University of London; 2011.
2018	Costa MC. Prediction of the Risk of Vertebral Fracture in Patients With Metastatic Bone Lesions as a Tool for More Effective Patients’ Management [PhD thesis]. University of Sheffield; November 2018.
2019	Nguyen C. Multiscale Network Characterization of the Strength and Robustness of Trabecular Bone [PhD thesis]. Santa Barbara, CA: Santa Barbara, University of California; September 2019.
2020	Belda González R. Mechanical and Morphometric Characterization of Cancellous Bone [PhD thesis]. Universität Politècnica de València; March 2020.
2009	Won E. Structural Effects of Photodynamic Therapy and Bisphosphonates on Healthy and Metastatically Involved Vertebral Bone [Master's thesis]. University of Toronto; 2009.
2011	Lo V. Short and Longer-Term Effects of Photodynamic Therapy and Combination Treatments on Healthy and Metastatically-Involved Vertebrae [Master's thesis]. University of Toronto; 2011.
2014	Choudhari C. Image-Based Characterization of the Mechanical Behaviour of Healthy and Metastatically-Involved Vertebrae [Master's thesis]. University of Toronto; 2014.
2018	Burke MV. Quantification of Changes in Vertebral Bone Quality in the Presence of Metastases [PhD thesis]. University of Toronto; 2018.
2019	Clement A. Image Based and Biomechanical Characterization of Osteoblastic Vertebral Metastases [Master's thesis]. University of Toronto; 2019.
2021	Kusins J. A Multi-Level Mechanical Assessment of the Shoulder Coupled With Evaluation of Upper Extremity Predictive Finite Element Models [PhD thesis]. University of Western Ontario; 2021.