Equivalent Twelve-Month Bone Mineral Density Response to Romosozumab in Patients Aged ≥ 85 Years and  < 85 Years: A Multi-center Real-World Cohort Study (n = 417) from Northern Japan.

Patients aged ≥ 85 years are systematically under-represented in pivotal romosozumab trials, yet bear the highest absolute fracture burden in aging societies. Whether romosozumab achieves equivalent bone mineral density (BMD) gains in this population remains unproven. We conducted a multi-center retrospective cohort study at two hospitals in Aomori Prefecture, Japan (Mutsu General Hospital and Towada City Hospital). All adult patients who initiated subcutaneous romosozumab 210 mg monthly for osteoporosis between April 2019 and April 2025 were included. The primary outcome was the percentage change in lumbar spine BMD (LS-BMD) at 12 months, compared between patients aged ≥ 85 years and < 85 years. Equivalence was prospectively assessed using two one-sided tests (TOST) with margins of ± 5 and ± 3% points. Pre-specified secondary analyses included 12-month bone turnover markers (P1NP and TRACP-5b), age × prior treatment interaction, and a concomitant vitamin D subgroup analysis. The analytic cohort comprised 417 patients (Mutsu 315, Towada 102; 346 aged < 85 years and 71 aged ≥ 85 years). Approximately 50% of patients in each stratum received a concomitant active vitamin D analog (< 85: 50.6%; ≥85: 53.5%). The median LS-BMD percentage change at 12 months was + 11.1% [IQR 6.3 to 17.5] in patients aged < 85 years (n = 337 with paired data) and + 10.9% [IQR 6.2 to 20.0] in patients aged ≥ 85 years (n = 69) (Mann-Whitney P = 0.926). The 90% confidence interval of the between-group difference lay entirely within both pre-specified equivalence margins (TOST P = 0.0009 at ± 5% points; P = 0.031 at ± 3% points). Total hip BMD change was also equivalent (TOST at ± 5 pp, P = 0.012). Bone turnover markers decreased similarly in both age strata (P1NP median - 16.4% vs. - 19.6%, P = 0.928; TRACP-5b - 32.1% vs. - 33.1%, P = 0.746). Concomitant vitamin D use did not modify the LS-BMD response in either stratum (both between-group P ≥ 0.27). A borderline age × prior-treatment interaction was observed (β = + 5.60 pp, P = 0.082): prior treatment attenuated the response in patients < 85 years (naïve + 14.6% vs. pretreated + 7.5%, P < 0.001) but not in patients ≥ 85 years (+ 10.7% vs. + 11.2%, P = 0.59). On-treatment fragility fracture rates were 5.2% (18/345) in < 85-year patients and 7.0% (5/71) in ≥ 85-year patients (Fisher P = 0.57), with similar renal function and calcium profiles. In this multi-center real-world cohort, twelve-month romosozumab response was statistically equivalent between patients aged ≥ 85 years and < 85 years at both pre-specified equivalence margins. The equivalence was robust to concomitant vitamin D status, was consistent at the total hip, and was corroborated by comparable bone turnover marker changes. The attenuating effect of prior treatment observed in < 85-year patients appeared to be absent in patients ≥ 85 years, a pattern that may reflect incomplete carry-over suppression of bone remodeling by prior therapy in the very elderly and that deserves further study. Romosozumab should not be withheld from very elderly patients on the basis of age alone.