The institutional review board or ethics committee at each site approved the study. The study was conducted in accordance with all country regulations,

the Declaration of Helsinki, and the International Conference on Harmonization Good Clinical Practice Guidelines. All subjects provided written informed consent prior to enrollment. Ultradistal radius images were acquired using Scanco HR-pQCT with an isotropic voxel size of 82 μm [16] and [17]. Cortical porosity was quantified at baseline, 6 and 12 months using StrAx1.0, a software able to automatically quantify the porosity within CAL101 the compact-appearing cortex and the outer and inner transitional zones of the cortex [18] and [19]. The outer transitional zone is trabecularized cortex adjacent to the compact-appearing cortex, while the inner transitional Epacadostat supplier zone is trabecularized cortex adjacent to the medullary cavity [19]. StrAx1.0 is available

as an online image analysis software (www.straximages.com). The method is accurate in measuring dimensions (total cross-sectional area, areas of compact-appearing cortex, transitional zones, and trabecular compartments) and porosity. The regression between the gold standard micro-CT and StrAx1.0 measurements from HRpQCT has an R2 ranging from 0.87 to 0.99. The regression between selleck gold standard scanning electron microscopy (SEM) and StrAx1.0 measurements from HRpQCT images has an R2 ranging from 0.91 to 0.99 for areas and porosity. Reproducibility expressed as the root mean square of the coefficient variation (RMS CV%) for areas and porosity measurements ranges from 0.54 to 3.98% [18]. Porosity was quantified as the percent of the total compartment volume occupied by void. Details and validation of the method of quantification of porosity using StrAx1.0 are published [16], [18], [19], [20] and [21]. To avoid overestimating

porosity by including under-mineralized bone matrix, quantification of porosity is confined to voxels with attenuation values less than 80% of that produced by fully mineralized bone. Voxels with attenuation values greater than 80% of that produced by fully mineralized bone were excluded from the analysis because pores only produce attenuation below 80% of maximum [19]. Voxels producing attenuation within 80% of maximum contain matrix that has undergone incomplete secondary mineralization (primary mineralization reaches 80% of maximum within a few days of matrix deposition). Thus, there is little, if any confounding effect of mineralization. Because StrAx1.