Assessing cortical bone changes with Romosozumab after one year: Insights from an exploratory HR-pQCT study

Purpose: To describe changes in bone microarchitecture after 6 and 12 months of romosozumab (ROMO), identify responders based on cortical thickness (Ct.Th) increase at the distal radius (≥3% at 12 months), and explore factors associated with treatment response. Methods: We conducted a prospective cohort study of postmenopausal women with osteoporosis at very high fracture risk who started ROMO between August 2021 and February 2023. HR-pQCT, BMD, and bone turnover markers were assessed at baseline, 6, and 12 months. Patients were classified as responders or non-responders based on 12-month Ct.Th changes. Results: Sixteen patients were analyzed. Although improvements in distal tibial microarchitecture were observed at 12 months, treatment responses were heterogeneous. Nine patients were classified as responders and seven as non-responders. Baseline characteristics were similar, though responders had lower trabecular bone parameters at the distal radius. At 12 months, responders showed significant gains in Ct.Th and cortical area at both distal tibia (+5% and + 5%) and radius (+7% and + 6%), while non-responders showed no improvement or decline. These trends were evident by 6 months. Lumbar spine and hip BMD increased significantly only in responders (+14% and + 6%). PTH levels rose in both groups at 6 months but continued increasing only in non-responders, despite comparable vitamin D status. Conclusion: By stratifying patients based on Ct.Th changes, we identified treatment responders (56%) with rapid cortical bone improvements detectable at 6 monthsIdentifying clinical predictors of ROMO responsiveness and determining whether shorter treatment durations may be justified in selected patients warrant further investigation.