SAT-721 Denosumab After Bariatric Surgery Increases Bone Mass, Microarchitecture, and Estimated Strength in Postmenopausal Women and Older Men: A Randomized Controlled Trial

Abstract Disclosure: K.C. Wu: None. C. Nevarez: None. L. Marion: None. E.H. Koh: None. G.H. Jung: None. N.J. King: None. C. Chan: None. A.L. Schafer: Amgen Inc, Bone Health Technologies Inc. E.W. Yu: Amgen Inc. Context: Bariatric surgery is an effective treatment for severe obesity but can lead to adverse skeletal effects with increased bone turnover, decreased bone mineral density (BMD), weakened bone microarchitecture, and increased fracture risk. Evidence-based interventions for preventing bone loss after bariatric surgery are lacking. In a randomized controlled trial, we recently demonstrated that denosumab (DMAB) treatment increased hip and spine BMD, without symptomatic or moderate/severe hypocalcemia. Objective: To examine the effects of DMAB, compared to placebo (PBO), on appendicular bone mass, microarchitecture, and estimated strength after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Design, Setting, Participants: Two-site, double-blind randomized placebo-controlled trial of 36 postmenopausal women and men ≥50 years receiving RYGB or SG. Participants were randomized 2:1 to receive either DMAB (60mg SC) or PBO every 6 months for 18 months starting 1 month after surgery. Calcium intake and vitamin D goals were standardized. Main Outcome Measures: High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia was performed at 1 and 19 months postoperatively. Between-group differences in percentage change for all bone measures were compared using analysis of covariance, adjusting for study site and surgery type. Results: The DMAB (n=24) and PBO (n=12) groups were similar in age (57±7 yrs), sex (67% women), preoperative BMI (44±6 kg/m2), and surgery type (72% SG). Both groups lost a similar amount of weight from baseline to 19 months (-25±15 kg). DMAB participants had an increase in total volumetric BMD at both anatomic sites, while the PBO participants had a decrease (+1.9% vs. -3.3% radius; +1.4% vs. -4.5% tibia; between-group difference p<0.01 for both). Compared to PBO, the DMAB group had improvements in cortical microarchitecture at both the tibia and radius with increased cortical area and thickness and decreased porosity (p≤0.01 for all). There were no significant between-group differences in trabecular microarchitecture including trabecular number and thickness. Estimated bone strength increased in the DMAB group compared to PBO at the tibia (failure load: +2.0% vs. -6.4%, p<0.01) but was not significantly different at the radius. Conclusion: Treatment with DMAB had a protective effect on appendicular bone mass and microarchitecture after bariatric surgery, at both weight bearing and non-weight bearing bones. Microarchitectural improvements were more marked in the cortical compartment than the trabecular. Estimated bone strength was preserved at the tibia with DMAB. DMAB may be an effective option to preserve bone integrity among postmenopausal women and men ≥50 years who are receiving bariatric surgery. Presentation: Saturday, July 12, 2025