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

Authors

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, Wright State University - Main CampusFollow
Donald S. Williams

Document Type

Article

Publication Date

6-2012

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 (r² = 0.95) of the UD radius. Single linear regressions of FEA-determined ultimate stress showed high correlation with HR-pQCT derived parameters: integral vBMD (r² = 0.86), bone volume fraction (r² = 0.84) and cortical thickness (r² = 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/cm³) 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.

Repository Citation

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 (6), 1379-1388.
https://corescholar.libraries.wright.edu/bie/126

DOI

10.1016/j.bone.2012.03.017