8455 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p<0.01), had longer diabetes duration (8.4 vs 7.2, p<0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p<0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024