Although bone mineral density (BMD) is a predictor of fracture, many fractures occur in women with T-scores >-2.5. Bone microarchitecture, assessed by trabecular bone score (TBS), predicts fracture risk independent of BMD. We evaluated whether abaloparatide improves TBS and whether TBS trends were associated with vertebral fracture risk reduction. Women with osteoporosis randomized to abaloparatide or placebo for 18 months (ACTIVE), followed by alendronate for 24 months (ACTIVExtend), with evaluable TBS, were included in this post hoc analysis (N=911). TBS was calculated from spine BMD scans using an algorithm adjusted for tissue thickness (TBS ) at baseline, 6, 18, and 43 months. Mean increments in TBS from baseline within and between treatment groups, proportion of women with TBSth increments above least significant change (LSC) and proportion with degraded TBS (<1.027) were calculated. Risk estimates for vertebral fracture were compared using binary logistic regressions adjusted for baseline age and spine BMD. At baseline, 42% had degraded TBS . Mean TBS increased 4% after 18 months abaloparatide (P<0.001) and was unchanged with placebo. After 2 subsequent years of alendronate, the total cumulative TBS increase was 4.4% with abaloparatide/alendronate and 1.7% with placebo/alendronate (group difference, P<0.001). At 43 months, the proportion of women with degraded TBS had declined to 21% with abaloparatide/alendronate and 37% with placebo/alendronate (P<0.05). An increase in TBS ≥LSC was observed in 50% of abaloparatide-treated women at 18 months and was associated with decreased odds (OR [95% CI]) of vertebral fracture (0.19 [0.04, 0.80], 6 months; 0.30 [0.11, 0.79], 43 months). In conclusion, abaloparatide increased TBS rapidly and progressively over 18 months and increments were maintained over 2 years with alendronate. TBS increase was associated with vertebral fracture risk reduction. Microarchitectural improvement may be one mechanism by which abaloparatide strengthens vertebral bone.This article is protected by copyright. All rights reserved.