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

详细信息	查看全文 | 推荐本文 |

• 作者：Richa Y. Jayakar^a ; ^{richa_jayakar@merck.com} ; Antonio Cabal^b ; ^{antonio_cabal@merck.com} ; John Szumiloski^c ; ^{john_szumiloski@merck.com} ; Swanand Sardesai^b ; ^{swanand_sardesai@merck.com} ; Eual A. Phillips^g ; ^{eual@seas.upenn.edu} ; Andres Laib^h ; ^{alaib@scanco.ch} ; Boyd B. Scott^d ; ^{boyd_scott@merck.com} ; Maureen Pickarski^f ; ^{Maureen_pickarski@merck.com} ; Le T. Duong^f ; ^{Le_duong@merck.com} ; Christopher T. Winkelmann^a ; ^{christopher.winkelmann@merck.com} ; Paul J. McCracken^a ; ¹ ; ^{Paul_McCracken@eisai.com} ; Richard Hargreaves^e ; ^{richard_hargreaves@merck.com} ; Thomas N. Hangartnerⁱ ; ^{thomas.hangartner@wright.edu} ; Donald S. Williams^a ; ^{donald_williams2@merck.com}
• 关键词：Imaging ; FEA ; Odanacatib ; HR-pQCT ; Bone microstructure
• 刊名：Bone
• 出版年：2012
• 期刊代码：39_87563282
• 类别：med
• 出版时间：June, 2012
• 卷：50
• 期：6
• 页码：1379-1388
• 文件大小：545 K

摘要

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 卤 27 vs. 364 卤 22 mg HA/cm³) and cortical thickness (Ct.Th) (0.90 卤 0.07 vs. 0.64 卤 0.04 mm) at the UD radius, Ct.Th (2.15 卤 0.28 vs. 1.56 卤 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.