RF30 | PSAT172 Effects of 12 Months of Alendronate Therapy Subsequent to 12 Months of Denosumab Administration in Women With Anorexia Nervosa
Authors: Haines Melanie , Kimball Allison , Meenaghan Erinne , Strauch Julianne , Colling Caitlin , Singhal Vibha , Eddy Kamryn , Misra Madhusmita , Miller Karen 
Published: November 2022

Abstract
Low bone mineral density (BMD) and increased fracture risk are common complications of anorexia nervosa. We assessed whether 12 months of alendronate subsequent to 12 months of denosumab would 1) maintain the increases in BMD observed with denosumab and 2) result in higher BMD than alendronate for 12 months alone in 30 ambulatory women with anorexia nervosa and areal BMD (aBMD) Z- or T-score &lt;-1.0. Participants were randomized in a 2: 1 ratio to 12 months of denosumab (60mg subcutaneously q6 months) followed by 12 months of open-label alendronate (70mg orally qweek)("denosumab-to-alendronate" n=20) or 12 months of subcutaneous placebo followed by 12 months of open-label alendronate (70mg orally qweek)("placebo-to-alendronate" n=10). The prespecified primary outcome was PA lumbar spine aBMD by DXA. Secondary outcome measures included tibial and radial volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral quantitative CT (HR-pQCT), and markers of bone turnover. Twelve-month results were reported in abstract form; 24-month results have not been published.
At baseline, mean age [29±8 y (mean±SD)], BMI (18.6±1.9 kg/m2), and aBMD (PA lumbar spine Z-score -1.6±1.1) were similar between groups. From 12 to 24 months in the denosumab-to-alendronate group, favorable changes in spine aBMD, radial vBMD, and radial and tibial microarchitecture from 12 months of denosumab were maintained after 12 months of alendronate. However, there was a rebound increase in markers of bone turnover (p&lt;0.003), and PA and lateral lumbar spine aBMD decreased in 6 and 9 participants, respectively. Both a greater suppression of bone turnover markers and a greater increase in aBMD from baseline to 12 months were predictors of partial reversal of BMD gains from 12 to 24 months in the denosumab-to-alendronate group. Over 24 months, PA lumbar spine aBMD (3.9±4.3%), femoral neck aBMD (3.1±5.5%), tibial vBMD and failure load increased within the denosumab-to-alendronate group, and PA lumbar spine aBMD (5.8±5.3%) increased within the placebo-to-alendronate group (p&lt;0.05). In a 24-month between-group comparison, there was no difference in change in aBMD at any site; however, the denosumab-to-alendronate group demonstrated favorable changes in tibial vBMD and trabecular microarchitecture compared to the placebo-to-alendronate group (p&lt;0.05).
In conclusion, this pilot study suggests that 12 months of alendronate maintains BMD gains achieved with 12 months of denosumab administration in some, but not all, women with anorexia nervosa. A more robust response to denosumab may be a risk factor for partial reversal of denosumab-related BMD gains despite alendronate. Therefore, a more effective antiresorptive agent may be necessary to maintain gains in BMD achieved with denosumab therapy in some women with anorexia nervosa. Moreover, sequential therapy of denosumab followed by alendronate over 24 months results in greater improvements in tibial vBMD and microarchitecture than 12 months of alendronate, although increases in aBMD were similar between groups.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:30 p.m. - 12:35 p.m.