High doses of olpadronate improve cortical bone toughness in intact retired-breeder rats without affecting mass, geometry, mineralization, and elastic properties.

MARÍA ANGELINA CHIAPPE; L ISLA; E DE SIMONE; EMILIO ROLDAN; GUSTAVO ROBERTO COINTRY; JOSÉ LUIS FERRETTI; RICARDO FRANCISCO CAPOZZA

Denver (CO)

Congreso; XXXI ANNUAL MEETING, American Society for Bone & Mineral Research (ASBMR).; 2009

High Doses of Alendronate Improve Cortical Bone Toughness In Intact Retired-Breeder Rats Without Affecting Mass, Geometry, Mineralization, and Elastic Properties Authors: A. Chiappe Barbará, L. Isla, E. De Simone, E. Roldan, G. Cointry, J. Ferretti, R. CapozzaA. Chiappe Barbará, L. Isla, E. De Simone, E. Roldan, G. Cointry, J. Ferretti, R. Capozza BP effects on bone post-yield behavior are scarcely studied. We analyzed alendronate effects on rat cortical bone mass, design, "quality" and strength including pre/post-yield behavior avoiding growth and hormonal interactions in female, retired-breeder Sprague-Dawley rats aged 13 mo (bw about 350g) treated with 0 (N=10), 5 (9), 25 (9) or 125 (10) mg/kg/d of alendronate 2d/wk during 12 weeks. Their femurs were pQCT-scanned (XCT-2000, Stratec) at mid-diaphysis to assess cortical bone mass (area, BMC; CtA, CtC), design (peri/endosteal perimeters; cortical thickness; bending and torsion crosssectional moments of inertia, xMI, yMI, pMI), bone material’s mineralization (cortical vBMD, vCtD) and diaphyseal strength (bending Bone Strength Index, xBSI=xMI*vCtD). Then the bones were assayed in 3-point bending (1mm/min strain rate) to determine bone displacement (d), reacting force (F), structural stiffness (F/d) and energy absorption (EA) at the yielding point (dy, Fy, Fy/dy, EAy) and at the maximumdisplacement point after yielding (dmax, Fmax, EAmax). The proportion between post/pre-yield EA (EAf/y=100*EAmax/EAy) and the elastic modulus of cortical bone(E=Fy/48dy*xMI) were calculated from the available data. No effects were observed on CtA, CtC, perimeters, thickness, MIs, vCtD and pre-yield properties (dy, Fy, Fy/dy, E, EAy) at any dose. Positive effects of only the highest dose were observed on Fmax (+27%) and all post-yield properties: dmax +31%, EAf +21%, EAf/y +230%, always p<0.001. The parallel, linear correlation curves between the mechanically-assayed Fmax (y) and the xBSI (x), expression of the predictive value of xBSI which disregards all determinants of cortical micro-structure, showed similar intercepts for 0, 5 and 25 groups and a higher intercept for the 125 group (p<0.001). Results indicate a positive effect of the highest assayed dose of alendronate on ultimate strength and all post-yield properties of bones, with no changes in bone mass, pre-yield properties, or cortical mineralization or stiffness (E). This excludes any effect on bone mass, geometry, material "quality" (as assessed) and resilience. Restriction of effects to post-yield properties, as well as the underestimation of ultimate strength by the BSI at that dose, suggests some positive alendronate effect on some micro-structural determinant(s) of bone toughness. The analysis of the attractive possibility to extrapolate these findings to human skeletons requires further investigation.