4A and B). The absolute increases from baseline observed in hip BMC at month 36 were 247 mg in the trabecular compartment, 108 mg in the subcortical compartment, and 456 mg in the cortical compartment in the denosumab-treated group. We undertook this analysis to further characterize compartmental changes associated with the observed improvements in aBMD previously documented by DXA with denosumab treatment at the total hip, in the context of the significant hip fracture reductions observed in the FREEDOM study [20]. MIAF provides a more comprehensive method

to evaluate integral and compartment changes Ipilimumab ic50 from QCT scans, including measuring changes within subregions of the cortex, evaluating the subcortical region, and quantifying cortical geometry. In this QCT MIAF substudy from FREEDOM, significant and selleckchem progressive increases in total hip integral vBMD and BMC were confirmed to result from significant corresponding gains across trabecular and cortical compartments at months 12, 24, and 36. The results extend the previously observed aBMD increases from other

phase 2 and phase 3 denosumab clinical trials that have measured bone mass using DXA [18], [19], [20] and [21]. The positive effect of denosumab on total hip integral vBMD and BMC is consistent with a recently reported study using MINDWAYS to analyze QCT scans [25]. However, results for the cortical compartment differ as the MINDWAYS analysis showed large increases with denosumab in cortical BMC and volume, but surprisingly not

in cortical BMD, suggesting that the increase in BMC was largely caused by an increase in cortical volume [25]. The MIAF analysis showed similar percentage changes for vBMD and BMC across all bone compartments indicating that volumes, in particular cortical volume, did not change substantially. This difference with respect to the MINDWAYS analysis is explained by the difference in segmentation approaches. Indeed, simulations explained that with a global threshold, as used N-acetylglucosamine-1-phosphate transferase by MINDWAYS, a longitudinal change in cortical BMD resulted in an artificial change in cortical volume, and therefore an exaggeration of the change in cortical BMC relative to the change in cortical BMD. Gains also were observed in the subcortical (transitional) compartment, a region also relevant to bone strength, and which may represent remnants of eroded cortical bone, the trabecular–cortical boundary, and/or cortical bone that has become “trabecularized” from endocortical and intracortical resorption. The absolute changes in cortical vBMD and BMC in subjects treated with denosumab were noteworthy and larger than those observed in the trabecular compartment.