ORF34-08 - Three Versus Twelve Months of Romosozumab for Postmenopausal Osteoporosis: The Limited Duration Anabolic Therapy (LIDA) Randomized Controlled Trial

Introduction:
Postmenopausal osteoporosis is associated with substantial morbidity, mortality, and healthcare costs. Romosozumab, the most recently approved osteoporosis drug, is a monoclonal antibody that increases bone mineral density (BMD) more than other agents by stimulating bone formation while inhibiting resorption. However, its anabolic effects are transient, diminishing after several months, whereas antiresorptive effects persist. The use of romosozumab is further limited by cost, injection burden, and a possible increased risk of cardiovascular adverse events. This trial evaluated whether a shorter course of romosozumab followed by antiresorptive therapy provides efficacy comparable to the standard 12-month romosozumab regimen.

Methods:
The Limited Duration Anabolic Therapy (LIDA) non-inferiority RCT randomized 50 postmenopausal women at high fracture risk to receive either 12 months of romosozumab or 3 months of romosozumab followed by 9 months of denosumab, all at FDA-approved doses. The primary endpoint was the 12-month change in total hip areal BMD (aBMD) measured by DXA. Secondary outcomes included aBMD at additional skeletal sites and high-resolution peripheral quantitative CT (HR-pQCT)–derived measures of volumetric BMD (vBMD), bone microarchitecture, and estimated strength at the distal tibia and radius (via finite element analysis).

Results:
The mean participant age was 69.6 years, and clinical characteristics were well matched at baseline. Mean (±SD) 12-month total hip aBMD increased by 5.7 ± 3.3% in the 3-month romosozumab group and 6.0 ± 3.2% in the 12-month group, meeting the prespecified non-inferiority margin of 2% (90% CI −1.2 to +1.9). Changes in aBMD at the femoral neck, lumbar spine, and distal radius were also similar between groups (5.0 ± 6.2% vs 6.3 ± 4.8%, 10.6 ± 5.4% vs 12.5 ± 4.4%, and −0.3 ± 2.6% vs −1.5 ± 3.0%, respectively; p=NS for all between-group comparisons).

Mean total vBMD increased more in the 3-month romosozumab group than the 12-month group at both the tibia (2.4 ± 1.7% vs 1.4 ± 2.1%, p=0.007) and radius (1.9% ± 2.1% vs 0.4% ± 2.8%, p=0.008). Gains in cortical and trabecular vBMD and estimated strength also favored the abbreviated regimen but were not statistically significant. Changes in cortical and trabecular microarchitecture were small and similar between groups.

Summary:
In postmenopausal women at high fracture risk, 3 months of romosozumab followed by 9 months of denosumab was non-inferior to 12 months of romosozumab in improving total hip aBMD, with similar effects at other skeletal sites. HR-pQCT measures of vBMD favored the abbreviated approach. These findings demonstrate that a shorter romosozumab regimen can achieve comparable skeletal benefits while reducing treatment burden, cost, and possible adverse cardiovascular events, supporting its use as an effective and pragmatic alternative in osteoporosis management.