5% for all outcomes [41]. In addition to the standard morphological analysis, we applied

a customized segmentation algorithm [37], [42] and [43] to the HR-pQCT scans to assess cortical BMD (Ct.BMD, mm HA/cm3), total cross-sectional area (Tt.Ar, mm2), cortical thickness (Ct.Th, mm) [44], and cortical porosity (Ct.Po, %) [37], [42] and [43]. This technique can reduce variation in Ct.Th measures caused by differences in degree of bone mineralization, which can be present when obtaining Ct.Th by dividing see more cortical bone volume by the periosteal surface. In vivo reproducibility for these cortical measures is < 2.9%, with the exception of Ct.Po, which has a reported least significant change of 0.58% for the radius and 0.84% for the tibia [42]. One trained technician analyzed all HR-pQCT scans. To obtain accurate estimates of bone strength, we used custom finite element analysis (FEA) software to analyze each HR-pQCT

scan based on a linear, homogenous model with a mesh generated using NVP-BGJ398 concentration the voxel conversion approach. This method incorporates the three-dimensional micro-architecture and local BMD of the scanned region of interest [45] and [46]. The models were solved using custom large-scale FEA software (Numerics88 Solutions, Calgary, Canada) [47] on a desktop workstation (Mac, OS X v10.5; 2 × 2.8 GHz Quad-Core Intel Xeon; 32 GB 800 MHz DDR2 FB-DIMM). Using this custom software, the radius and tibia models required an average of 60 min each to solve. The primary outcome was failure load (N), based on simulating axial compressive loading of the bone to 1% strain Olopatadine [48]. A Biodex isokinetic dynamometer (Biodex®, System 3, New York, USA) was used to measure maximal isokinetic knee extension and flexion torque (Nm) of the dominant leg. The Biodex seat was adjusted until the popliteal crease was at the edge of the chair and the axis of rotation was at the level of the femoral condyle. The leg pad was placed just above the malleoli. Participants began each test with their leg in a flexed position and commenced

with knee extension at 90°/s. Once the participant reached the point of maximum extension they immediately reverted to knee flexion also at 90°/s. The combination of extension and flexion consisted of one practice trial followed by three experimental trials with no rest. A digital low-pass filter with a cut-off frequency of 5 Hz reduced noise. This test is highly reliable [49] and targets large muscle groups such as the quadriceps and hamstrings that insert on the proximal tibia. A grip strength dynamometer (Almedic, Quebec, Canada) was used to determine overall isometric strength (kg) of the hand and forearm muscles of the dominant arm (or non-dominant for those participants with previous forearm fractures) using the Canadian Physical Activity, Fitness, and Lifestyle Approach protocol [50].