@entity171 (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to @entity235 . Although BPs also reduce toughness in the cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than the bone's material properties. Our lab has conducted several studies in which @entity235 were treated with @entity561 at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of @entity561 on toughness of the cortical bone. This analysis seemed particularly relevant given the recent occurrence of @entity3330 in @entity1 . Differences in the toughness of ribs taken from @entity235 derived from five separate experiments were measured. The @entity235 were orally administered saline (CON, 1ml/kg/day) or @entity561 ( @entity16292 ) at a clinical dose (0.2mg/kg/day). Treatment duration ranged from 3months to 3years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and @entity16292 at each time point revealed a significant reduction in toughness with longer exposure to @entity16292 . The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of @entity16292 results in @entity79 in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical @entity174 of the femoral cortical bone in @entity1 .

Duration-dependent effects of clinically relevant oral XXXX doses on cortical bone toughness in @entity235 .

@entity1 :: ('9606', 'Species') :: ['humans'] @entity171 :: ('MESH:D004164', 'Chemical') :: ['Bisphosphonates'] @entity174 :: ('MESH:D050723', 'Disease') :: ['fractures'] @entity235 :: ('9615', 'Species') :: ['dogs'] @entity561 :: ('MESH:D019386', 'Chemical') :: ['alendronate'] @entity16292 :: ('CHEBI:50878', 'Chemical') :: ['ALN'] @entity79 :: ('MESH:D001847', 'Disease') :: ['deterioration of cortical bone toughness'] @entity3330 :: ('MESH:D005264', 'Disease') :: ['atypical femoral fractures']
@entity561 :: (MESH:D019386,Chemical) :: ['alendronate']
