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1 Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU 2 Endocrinology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU 3 University of Toronto 4 unknown 5 Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
Improvements in Bone Geometry, Microarchitecture and Estimated Bone Strength
The cathepsin K inhibitor odanacatib, currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal BMD at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double-blind, placebo-controlled trial, using both quantitative computed tomography (QCT) and high resolution-peripheral (HR-p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here we report the results of HR-pQCT assessment. 214 postmenopausal women (mean age 64.0 ± 6.8 years, and baseline lumbar spine T-score -1.81 ± 0.83) were randomized to oral ODN 50 mg or PBO weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also seen in trabecular vBMD, cortical vBMD, cortical thickness, cortical area and strength (failure load) estimated using finite element analysis of HR-pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and BV/TV versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity seen with placebo (treatment difference= -7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research.
Journal of Bone and Mineral Research, 2014, Vol 29, Issue 8
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