Image Based and Biomechanical Characterization of Osteoblastic Vertebral Metastases

The negative consequences of fracture in the metastatic spine motivates improved bone quality assessment and fracture risk prediction. This study aims to automate preclinical microcomputed tomography (µCT) image identification of osteoblastic metastatic disease in vertebrae, characterize how metastases affect the material/mechanical properties of bone tissue and extend finite element (FE) modeling to include pathological changes to evaluate damage and fracture behaviour. A combination of image analysis techniques (µCT-based stereological analysis, back scatter electron microscopy) and computational modeling (voxel-based µFE modeling of postyield mechanical behaviour experimentally validated through sequentially imaged mechanical testing) is used to characterize the structural and material level impact of osteoblastic disease in vertebral trabecular bone. Methods for automated segmentation of osteoblastic lesions are also developed with µCT feature extraction and random forest classification methods to enable identification of pathologic tissue. Advanced preclinical understanding of osteoblastic disease can provide a foundation for improved guidelines for clinical treatment decision-making

Year	Entry
2013	Harrison NM, McDonnell P, Mullins L, Wilson N, O’Mahoney D, McHugh PE. Failure modelling of trabecular bone using a non-linear combined damage and fracture voxel finite element approach. Biomech Model Mechanobiol. April 2013;12(2):225-241.
2006	Ural A, Vashishth D. Cohesive finite element modeling of age-related toughness loss in human cortical bone. J Biomech. 2006;39(16):2974-2982.
2010	Roux J-P, Wegrzyn J, Arlot ME, Guyen O, Delmas PD, Chapurlat R, Bouxsein ML. Contribution of trabecular and cortical components to biomechanical behavior of human vertebrae: an ex vivo study. J Bone Miner Res. February 2010;25(2):356-361.
1998	Roschger P, Fratzl P, Eschberger J, Klaushofer K. Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies. Bone. October 1998;23(4):319-326.
1993	Grynpas M. Age and disease-related changes in the mineral of bone. Calcif Tiss Int. February 1993;53(suppl 1):S57-S64.
2003	Roschger P, Gupta HS, Berzlanovich A, Ittner G, Dempster DW, Fratzl P, Cosman F, Parisien M, Lindsay R, Nieves JW, Klaushofer K. Constant mineralization density distribution in cancellous human bone. Bone. March 2003;32(3):316-323.
2013	Hambli R. Micro-CT finite element model and experimental validation of trabecular bone damage and fracture. Bone. October 2013;56(2):363-374.
2008	Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. March 2008;42(3):456-466.
1998	Weiner S, Wagner HD. The material bone: structure-mechanical function relations. Ann Rev Mater Sci. August 1998;28:271-298.
2004	Oliver WC, Pharr GM. Measurement of hardness and elastic modulus by instrumented indentation: advances in understanding and refinements to methodology. J Mater Res. January 2004;19(1):3-20.
2011	Donnelly E. Methods for assessing bone quality: a review. Clin Orthop Relat Res. August 2011;469:2128-2138.
2007	Ruffoni D, Fratzl P, Roschger P, Klaushofer K, Weinkamer R. The bone mineralization density distribution as a fingerprint of the mineralization process. Bone. May 2007;40(5):1308-1319.
2018	Morton JJ, Bennison M, Lievers WB, Waldman SD, Pilkey AK. Failure behaviour of rat vertebrae determined through simultaneous compression testing and micro-CT imaging. J Mech Behav Biomed Mater. March 2018;79:73-82.
1987	Reid SA, Boyde A. Changes in the mineral density distribution in human bone with age: image analysis using backscattered electrons in the SEM. J Bone Miner Res. February 1987;2(1):13-22.
2008	Nazarian A, von Stechow D, Zurakowski D, Müller R, Snyder BD. 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.
1997	Yingling VR, Callaghan JP, McGill SM. Dynamic loading affects the mechanical properties and failure site of porcine spines. Clin Biomech (Bristol, Avon). July 1997;12(5):301-305.
2010	Cory E, Nazarian A, Entezari V, Vartanians V, Müller R, Snyder BD. Compressive axial mechanical properties of rat bone as functions of bone volume fraction, apparent density and micro-CT based mineral density. J Biomech. March 22, 2010;43(5):953-960.
2011	Renders GAP, Mulder L, van Ruijven LJ, Langenbach GEJ, van Eijden TMGJ. Mineral heterogeneity affects predictions of intratrabecular stress and strain. J Biomech. February 3, 2011;44(3):402-407.
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.
2006	Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength. Osteoporos Int. March 2006;17(3):319-336.
2006	Hadjidakis DJ, Androulakis II. Bone remodeling. Annals NY Acad Sci. December 2006;1092(1):385-396.
2001	Tanck E, Homminga J, van Lenthe GH, Huiskes R. Increase in bone volume fraction precedes architectural adaptation in growing bone. Bone. June 2001;28(6):650-654.
1998	Rho J-Y, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys. 1998;20(2):92-102.

Year

Entry

2013

Harrison NM, McDonnell P, Mullins L, Wilson N, O’Mahoney D, McHugh PE. Failure modelling of trabecular bone using a non-linear combined damage and fracture voxel finite element approach. Biomech Model Mechanobiol. April 2013;12(2):225-241.

2006

Ural A, Vashishth D. Cohesive finite element modeling of age-related toughness loss in human cortical bone. J Biomech. 2006;39(16):2974-2982.

2010

Roux J-P, Wegrzyn J, Arlot ME, Guyen O, Delmas PD, Chapurlat R, Bouxsein ML. Contribution of trabecular and cortical components to biomechanical behavior of human vertebrae: an ex vivo study. J Bone Miner Res. February 2010;25(2):356-361.

1998

Roschger P, Fratzl P, Eschberger J, Klaushofer K. Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies. Bone. October 1998;23(4):319-326.

1993

Grynpas M. Age and disease-related changes in the mineral of bone. Calcif Tiss Int. February 1993;53(suppl 1):S57-S64.

2003

Roschger P, Gupta HS, Berzlanovich A, Ittner G, Dempster DW, Fratzl P, Cosman F, Parisien M, Lindsay R, Nieves JW, Klaushofer K. Constant mineralization density distribution in cancellous human bone. Bone. March 2003;32(3):316-323.

2013

Hambli R. Micro-CT finite element model and experimental validation of trabecular bone damage and fracture. Bone. October 2013;56(2):363-374.

2008

Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. March 2008;42(3):456-466.

1998

Weiner S, Wagner HD. The material bone: structure-mechanical function relations. Ann Rev Mater Sci. August 1998;28:271-298.

2004

Oliver WC, Pharr GM. Measurement of hardness and elastic modulus by instrumented indentation: advances in understanding and refinements to methodology. J Mater Res. January 2004;19(1):3-20.

2011

Donnelly E. Methods for assessing bone quality: a review. Clin Orthop Relat Res. August 2011;469:2128-2138.

2007

Ruffoni D, Fratzl P, Roschger P, Klaushofer K, Weinkamer R. The bone mineralization density distribution as a fingerprint of the mineralization process. Bone. May 2007;40(5):1308-1319.

2018

Morton JJ, Bennison M, Lievers WB, Waldman SD, Pilkey AK. Failure behaviour of rat vertebrae determined through simultaneous compression testing and micro-CT imaging. J Mech Behav Biomed Mater. March 2018;79:73-82.

1987

Reid SA, Boyde A. Changes in the mineral density distribution in human bone with age: image analysis using backscattered electrons in the SEM. J Bone Miner Res. February 1987;2(1):13-22.

2008

Nazarian A, von Stechow D, Zurakowski D, Müller R, Snyder BD. 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.

1997

Yingling VR, Callaghan JP, McGill SM. Dynamic loading affects the mechanical properties and failure site of porcine spines. Clin Biomech (Bristol, Avon). July 1997;12(5):301-305.

2010

Cory E, Nazarian A, Entezari V, Vartanians V, Müller R, Snyder BD. Compressive axial mechanical properties of rat bone as functions of bone volume fraction, apparent density and micro-CT based mineral density. J Biomech. March 22, 2010;43(5):953-960.

2011

Renders GAP, Mulder L, van Ruijven LJ, Langenbach GEJ, van Eijden TMGJ. Mineral heterogeneity affects predictions of intratrabecular stress and strain. J Biomech. February 3, 2011;44(3):402-407.

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.

2006

Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength. Osteoporos Int. March 2006;17(3):319-336.

2006

Hadjidakis DJ, Androulakis II. Bone remodeling. Annals NY Acad Sci. December 2006;1092(1):385-396.

2001

Tanck E, Homminga J, van Lenthe GH, Huiskes R. Increase in bone volume fraction precedes architectural adaptation in growing bone. Bone. June 2001;28(6):650-654.

1998

Rho J-Y, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys. 1998;20(2):92-102.

Year	Entry
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.

Year

Entry

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.