Romosozumab Improves Microarchitecture as Assessed by Tissue Thickness-Adjusted Trabecular Bone Score in Postmenopausal Women with Osteoporosis.

Bone mineral density (BMD) is only one of several bone strength determinants affected by osteoporosis therapies. Trabecular Bone Score (TBS), a gray-level texture index determined from lumbar spine (LS) dual-X-ray absorptiometry scans, is an indirect measure of bone microarchitecture independent of and complementary to BMD and clinical risk factors. In the ARCH study, monthly subcutaneous romosozumab 210 mg for 12 months followed by 24-month open-label weekly oral alendronate 70 mg (romosozumab-to-alendronate) significantly reduced fracture risk compared to 36-month alendronate alone in postmenopausal women with osteoporosis and prior fracture. This analysis evaluated tissue thickness-adjusted TBS (TBSTT) in a subgroup of patients from ARCH who had post-hoc TBS measurements at baseline and at least one post-baseline visit at Months 12, 24, and 36. Baseline characteristics were similar between romosozumab-to-alendronate (n = 190) and alendronate alone (n = 188). Romosozumab led to significantly greater gains in TBSTT vs alendronate at Month 12 (least squares mean difference, 3.6%), with greater gains maintained after transition to alendronate and persisting at Months 24 (2.9%) and 36 (2.3%; all P < 0.001). Romosozumab-to-alendronate increased the percentage of individual patients with "normal" TBSTT from 28.9% at baseline to 48.1%, 43.9%, and 45.4% at Months 12, 24, and 36, respectively, and decreased the percentage of individual patients with degraded TBSTT from 52.6% to 33.3%, 36.0%, and 33.5%, respectively (all P < 0.001). A similar but much smaller trend was observed with alendronate alone from baseline through Month 36 (P ≤ 0.012). Percent changes in TBSTT and LS BMD were largely unrelated from baseline to Month 12 (romosozumab-to-alendronate, r2 = 0.065; alendronate alone, r2 = 0.021) and Month 36 (r2 = 0.058; r2 = 0.057, respectively). In postmenopausal women with osteoporosis and prior fracture, 12-month romosozumab followed by 24-month alendronate significantly improved bone microarchitecture estimated by TBSTT more than 36-month alendronate alone.