MON-795 - Zoledronic Acid Maintains Gains in Spine and Hip Bone Mineral Density Achieved with Romosozumab in Women with Anorexia Nervosa

Low bone mineral density (BMD) is a common complication of anorexia nervosa, with no FDA-approved therapies. Our aim was to determine whether off-label administration of romosozumab, which addresses both the low bone formation and high bone resorption observed in anorexia nervosa, increases BMD (part 1), and whether zoledronic acid would maintain this increase (part 2). We reported part 1 at ENDO 2025 and now report the part 2 results. This was a 24-month, randomized, placebo-controlled study of 30 women with low-weight or atypical (normal-weight) anorexia nervosa, ages 20-60 y, with low BMD (Z-score < -1.0). Participants were randomized 2:1 to 12 months of romosozumab (210 mg SQ q4 weeks) (part 1) followed by 1 dose of zoledronic acid 5mg IV (ROMO-Z) (part 2), or 12 months of placebo (part 1) followed by 1 dose of zoledronic acid 5mg IV (PBO-Z) (part 2). The primary outcome measure was % change in postero-anterior (PA) lumbar spine BMD by DXA. Data analysis was performed using a mixed effects model using 0, 6, 12, and 24-month data.
Pre-treatment mean age [34 ± 13 (ROMO-Z) vs 27 ± 6 y (PBO-Z) (mean ± SD)], BMI (19.2 ± 2.2 vs 18.8 ± 1.2 kg/m2), and BMD (PA spine Z-score -1.6 ± 0.9 vs -2.0 ± 0.6) were similar between groups; BMI remained stable through the study. As previously reported, part 1 of the study demonstrated significant BMD gains, except at the radius, after 12 months of ROMO vs PBO of 13.6 ± 4.6% vs -0.2 ± 3.6% (p < 0.0001) at the PA spine, 19.1 ± 8.1% vs -0.3 ± 4.6% (p < 0.0001) at the lateral spine, 4.2 ± 4.0% vs 1.2 ± 2.7% (p=0.04) at the total hip, and 5.6 ± 5.3% vs -0.2 ± 4.6% (p=0.007) at the femoral neck. After zoledronic acid administration (part 2), from 12 to 24 months, BMD was maintained in the ROMO-Z, and increased in the PBO-Z, group at all sites (p < 0.02) except for the radius, resulting in cumulative increases in the ROMO-Z vs PBO-Z group over the full 24-month study of 14.8 ± 5.2 vs 4.4 ± 5.6% (p < 0.0001) at the PA lumbar spine, 17.8 ± 8.0 vs 4.2 ± 7.3% (p=0.0003) at the lateral lumbar spine and 6.3 ± 4.8 vs 2.6 ± 4.1%, p=0.034 at the femoral neck. There was no difference between groups at the total hip nor radius. From 12 to 24 months, serum CTX decreased in the PBO-Z vs ROMO-Z group (-27.9 ± 40.7 vs 12.9 ± 104.0%, p=0.012), and there was no change in P1NP (after a 3-month increase in the ROMO group, which was previously reported). At 24 months, in the ROMO-Z group, mean PA lumbar spine BMD Z-score was -0.3 ± 1.0, and the percent of subjects with PA lumbar spine BMD Z-score ≤ -1.0 decreased by 72%. Romosozumab was well tolerated; 64% of participants had flu-like symptoms after receiving zoledronic acid.
In conclusion, a single dose of zoledronic acid maintained gains in spine and hip BMD achieved with romosozumab in women with anorexia nervosa, increasing BMD Z-score to > -1 in 72% of women and resulting in a mean 15% increase in PA spine BMD with romosozumab followed by zoledronic acid vs a 4% increase in those who received placebo followed by zoledronic acid.

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