Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey

Richa Y. Jayakar; Antonio Cabal; John Szumiloski; Swanand Sardesai; Eual A. Phillips; Andres Laib; Boyd B. Scott; Maureen Pickarski; Le T. Duong; Christopher T. Winkelmann; Paul J. McCracken; Richard Hargreaves; Thomas N. Hangartner; Donald S. Williams

doi:10.1016/j.bone.2012.03.017

Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey

Richa Y. Jayakar, Antonio Cabal, John Szumiloski, Swanand Sardesai, Eual A. Phillips, Andres Laib, Boyd B. Scott, Maureen Pickarski, Le T. Duong, Christopher T. Winkelmann, Paul J. McCracken, Richard Hargreaves, Thomas N. Hangartner, Donald S. Williams

Wright State University

Research output: Contribution to journal › Article › peer-review

Abstract

This study aimed to validate finite element analysis (FEA) estimation of strength, identify high-resolution peripheral quantitative computed tomography (HR-pQCT) measures correlating with strength, and evaluate the precision of HR-pQCT measurements to longitudinally monitor effects of osteoporosis treatment in ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in three groups of NHPs: Intact (n = 10), OVX-odanacatib treated (OVX-ODN 30 mg/kg, n = 10) and OVX-vehicle treated (OVX-Veh, n = 10) at the ultradistal (UD) and distal 1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using the Pistoia criterion were validated by ex-vivo mechanical compression (r ² = 0.95) of the UD radius. Single linear regressions of FEA-determined ultimate stress showed high correlation with HR-pQCT derived parameters: integral vBMD (r ² = 0.86), bone volume fraction (r ² = 0.84) and cortical thickness (r ² = 0.79). Precision of HR-pQCT measurements, obtained from an excised radius and tibia, showed low variation (CV = 0.005%–5.6%) and helped identify possible sources of error. Comparison of OVX-Veh and Intact groups showed decreases in bone parameters demonstrating trends consistent with bone loss. Comparison of OVX-ODN and OVX-Veh groups showed a treatment effect with increases in bone parameters: integral vBMD (477 ± 27 vs. 364 ± 22 mg HA/cm ³ ) and cortical thickness (Ct.Th) (0.90 ± 0.07 vs. 0.64 ± 0.04 mm) at the UD radius, Ct.Th (2.15 ± 0.28 vs. 1.56 ± 0.08 mm) at the distal 1/3 radius. Axial compression peak stress calculated and obtained experimentally showed the OVX-ODN group was 33% stronger than the OVX-Veh group. We conclude that HR-pQCT and FEA serve as robust techniques to longitudinally monitor bone parameters and strength in NHP's.

Original language	American English
Journal	Bone
Volume	50
DOIs	https://doi.org/10.1016/j.bone.2012.03.017
State	Published - Jun 1 2012

Keywords

Bone Microstructure
FEA
HR-pQCT
Imaging
Odanacatib

Disciplines

Biomedical Engineering and Bioengineering
Engineering
Industrial Engineering
Operations Research, Systems Engineering and Industrial Engineering

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10.1016/j.bone.2012.03.017License: Unspecified

Cite this

Jayakar, R. Y., Cabal, A., Szumiloski, J., Sardesai, S., Phillips, E. A., Laib, A., Scott, B. B., Pickarski, M., Duong, L. T., Winkelmann, C. T., McCracken, P. J., Hargreaves, R., Hangartner, T. N., & Williams, D. S. (2012). Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey. Bone, 50. https://doi.org/10.1016/j.bone.2012.03.017

Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey. / Jayakar, Richa Y.; Cabal, Antonio; Szumiloski, John et al.
In: Bone, Vol. 50, 01.06.2012.

Research output: Contribution to journal › Article › peer-review

Jayakar, RY, Cabal, A, Szumiloski, J, Sardesai, S, Phillips, EA, Laib, A, Scott, BB, Pickarski, M, Duong, LT, Winkelmann, CT, McCracken, PJ, Hargreaves, R, Hangartner, TN & Williams, DS 2012, 'Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey', Bone, vol. 50. https://doi.org/10.1016/j.bone.2012.03.017

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title = "Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey",

abstract = " This study aimed to validate finite element analysis (FEA) estimation of strength, identify high-resolution peripheral quantitative computed tomography (HR-pQCT) measures correlating with strength, and evaluate the precision of HR-pQCT measurements to longitudinally monitor effects of osteoporosis treatment in ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in three groups of NHPs: Intact (n = 10), OVX-odanacatib treated (OVX-ODN 30 mg/kg, n = 10) and OVX-vehicle treated (OVX-Veh, n = 10) at the ultradistal (UD) and distal 1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using the Pistoia criterion were validated by ex-vivo mechanical compression (r 2 = 0.95) of the UD radius. Single linear regressions of FEA-determined ultimate stress showed high correlation with HR-pQCT derived parameters: integral vBMD (r 2 = 0.86), bone volume fraction (r 2 = 0.84) and cortical thickness (r 2 = 0.79). Precision of HR-pQCT measurements, obtained from an excised radius and tibia, showed low variation (CV = 0.005%–5.6%) and helped identify possible sources of error. Comparison of OVX-Veh and Intact groups showed decreases in bone parameters demonstrating trends consistent with bone loss. Comparison of OVX-ODN and OVX-Veh groups showed a treatment effect with increases in bone parameters: integral vBMD (477 ± 27 vs. 364 ± 22 mg HA/cm 3 ) and cortical thickness (Ct.Th) (0.90 ± 0.07 vs. 0.64 ± 0.04 mm) at the UD radius, Ct.Th (2.15 ± 0.28 vs. 1.56 ± 0.08 mm) at the distal 1/3 radius. Axial compression peak stress calculated and obtained experimentally showed the OVX-ODN group was 33% stronger than the OVX-Veh group. We conclude that HR-pQCT and FEA serve as robust techniques to longitudinally monitor bone parameters and strength in NHP's.",

keywords = "Bone Microstructure, FEA, HR-pQCT, Imaging, Odanacatib",

author = "Jayakar, {Richa Y.} and Antonio Cabal and John Szumiloski and Swanand Sardesai and Phillips, {Eual A.} and Andres Laib and Scott, {Boyd B.} and Maureen Pickarski and Duong, {Le T.} and Winkelmann, {Christopher T.} and McCracken, {Paul J.} and Richard Hargreaves and Hangartner, {Thomas N.} and Williams, {Donald S.}",

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doi = "10.1016/j.bone.2012.03.017",

language = "American English",

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T1 - Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey

AU - Jayakar, Richa Y.

AU - Cabal, Antonio

AU - Szumiloski, John

AU - Sardesai, Swanand

AU - Phillips, Eual A.

AU - Laib, Andres

AU - Scott, Boyd B.

AU - Pickarski, Maureen

AU - Duong, Le T.

AU - Winkelmann, Christopher T.

AU - McCracken, Paul J.

AU - Hargreaves, Richard

AU - Hangartner, Thomas N.

AU - Williams, Donald S.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - This study aimed to validate finite element analysis (FEA) estimation of strength, identify high-resolution peripheral quantitative computed tomography (HR-pQCT) measures correlating with strength, and evaluate the precision of HR-pQCT measurements to longitudinally monitor effects of osteoporosis treatment in ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in three groups of NHPs: Intact (n = 10), OVX-odanacatib treated (OVX-ODN 30 mg/kg, n = 10) and OVX-vehicle treated (OVX-Veh, n = 10) at the ultradistal (UD) and distal 1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using the Pistoia criterion were validated by ex-vivo mechanical compression (r 2 = 0.95) of the UD radius. Single linear regressions of FEA-determined ultimate stress showed high correlation with HR-pQCT derived parameters: integral vBMD (r 2 = 0.86), bone volume fraction (r 2 = 0.84) and cortical thickness (r 2 = 0.79). Precision of HR-pQCT measurements, obtained from an excised radius and tibia, showed low variation (CV = 0.005%–5.6%) and helped identify possible sources of error. Comparison of OVX-Veh and Intact groups showed decreases in bone parameters demonstrating trends consistent with bone loss. Comparison of OVX-ODN and OVX-Veh groups showed a treatment effect with increases in bone parameters: integral vBMD (477 ± 27 vs. 364 ± 22 mg HA/cm 3 ) and cortical thickness (Ct.Th) (0.90 ± 0.07 vs. 0.64 ± 0.04 mm) at the UD radius, Ct.Th (2.15 ± 0.28 vs. 1.56 ± 0.08 mm) at the distal 1/3 radius. Axial compression peak stress calculated and obtained experimentally showed the OVX-ODN group was 33% stronger than the OVX-Veh group. We conclude that HR-pQCT and FEA serve as robust techniques to longitudinally monitor bone parameters and strength in NHP's.

AB - This study aimed to validate finite element analysis (FEA) estimation of strength, identify high-resolution peripheral quantitative computed tomography (HR-pQCT) measures correlating with strength, and evaluate the precision of HR-pQCT measurements to longitudinally monitor effects of osteoporosis treatment in ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in three groups of NHPs: Intact (n = 10), OVX-odanacatib treated (OVX-ODN 30 mg/kg, n = 10) and OVX-vehicle treated (OVX-Veh, n = 10) at the ultradistal (UD) and distal 1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using the Pistoia criterion were validated by ex-vivo mechanical compression (r 2 = 0.95) of the UD radius. Single linear regressions of FEA-determined ultimate stress showed high correlation with HR-pQCT derived parameters: integral vBMD (r 2 = 0.86), bone volume fraction (r 2 = 0.84) and cortical thickness (r 2 = 0.79). Precision of HR-pQCT measurements, obtained from an excised radius and tibia, showed low variation (CV = 0.005%–5.6%) and helped identify possible sources of error. Comparison of OVX-Veh and Intact groups showed decreases in bone parameters demonstrating trends consistent with bone loss. Comparison of OVX-ODN and OVX-Veh groups showed a treatment effect with increases in bone parameters: integral vBMD (477 ± 27 vs. 364 ± 22 mg HA/cm 3 ) and cortical thickness (Ct.Th) (0.90 ± 0.07 vs. 0.64 ± 0.04 mm) at the UD radius, Ct.Th (2.15 ± 0.28 vs. 1.56 ± 0.08 mm) at the distal 1/3 radius. Axial compression peak stress calculated and obtained experimentally showed the OVX-ODN group was 33% stronger than the OVX-Veh group. We conclude that HR-pQCT and FEA serve as robust techniques to longitudinally monitor bone parameters and strength in NHP's.

KW - Bone Microstructure

KW - FEA

KW - HR-pQCT

KW - Imaging

KW - Odanacatib

UR - https://corescholar.libraries.wright.edu/bie/126

U2 - 10.1016/j.bone.2012.03.017

DO - 10.1016/j.bone.2012.03.017

M3 - Article

VL - 50

JO - Bone

JF - Bone

ER -

Evaluation of High-Resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-Clinical Model of Osteoporosis: A Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey

Abstract

Keywords

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