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In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high-dose (HD, 40-μg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard-dose teriparatide (SD, 20-μg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20-ug (n=39) or 40-μg (n=37) during months 0-9 overlapped with denosumab 60-mg s.c. given at month 3 and 9, for a 15-month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD-group than the SD-group at the distal tibia (5.3% vs. 3.4%, P=0.01) with a similar trend at the distal radius (2.6% vs. 1.0%, P=0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of -0.1% and -0.7% at the distal tibia and -0.4% and -0.1% at the distal radius, in the HD-group and SD-group, respectively, P=NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% (P<0.0001 vs. baseline) and 1.5% (P<0.0001 vs. baseline) in the HD-group and SD-group, respectively, P=0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro-finite element analysis at both sites were numerically greater in the HD-group compared to SD-group, but not significantly so. Together, these findings suggest that short-term treatment combining denosumab with either high or standard-dose teriparatide improves HR-pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD-group, which may be of benefit in postmenopausal women with severe osteoporosis. This article is protected by copyright. All rights reserved. |
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