There is increasing evidence that both trabecular and cortical bone are important determinants of strength in patients with osteoporosis who experience fracture [3], [4], [5] and [6]. Assessing both trabecular and cortical bone is important as these compartments may lose or gain bone differently with aging and in response to therapies, impacting their specific relative contributions to bone strength [7], [8] and [9]. The amounts of

both trabecular and cortical bone decrease as osteoporosis progresses; however, as trabecular bone disappears with increasing bone loss, the extent to which the cortical compartment contributes to bone strength increases [8], [9] and [10]. Use of new image acquisition and analysis techniques can provide information on the effects of treatments on bone density and geometrical changes in the trabecular and cortical compartments. Quantitative computed tomography (QCT) complements DXA by selleck chemical 3-dimensionally measuring TGFbeta inhibitor volumetric BMD (vBMD) and bone mineral content (BMC), commonly referred to as bone mass; these can be measured not only within the total bone

but also separately in the individual bone compartments [2] and [11]. Denosumab (Prolia®; Amgen Inc., Thousand Oaks, CA, USA) is a fully human monoclonal antibody that inhibits RANKL, a key modulator of osteoclast formation, function, and survival [12], [13], [14] and [15]. The mechanism of action of denosumab leads Liothyronine Sodium to rapid and maximal reductions in bone resorption throughout the trabecular and cortical compartments [16]. Clinical trials, including

the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study, have established that denosumab treatment results in a significant improvement in DXA aBMD at the hip in the majority of subjects [17], [18], [19], [20], [21], [22] and [23], and these gains significantly explained the observed fracture risk reductions [24]. Areal BMD gains are influenced by both trabecular and cortical changes, which cannot be precisely distinguished with DXA. In view of the strong association between gains in aBMD and the fracture risk reductions observed with denosumab treatment, and that both trabecular and cortical bone determine whole-bone strength, we have hypothesized and previously demonstrated using standard QCT analysis software that total hip BMD changes associated with denosumab would be apparent in both the trabecular and cortical compartments [25]. To further document and characterize the magnitude and distribution of the changes in BMD and BMC at the hip, and understand the relative contribution of each compartment, including the subcortical compartment, we applied Medical Image Analysis Framework (MIAF) software to hip QCT scans obtained in a subset of women who participated in the FREEDOM study. MIAF improves the 3D segmentation of the hip, and thus provides a more comprehensive method to evaluate integral and compartment changes [26] and [27].