Abstract Disclosure: S.K. Bhadada: None. L. Das: None. M. Baruah: None. V. Singla: None. V. Dhiman: None. S. Ram: None. S. Sharma: None. N. Sachdeva: None. P. Dutta: None. Introduction: Evidence is limited and there is no consensus about the effects of SGLT2i on bone metabolism. The objective of the current study was to assess changes in bone mineral density (BMD), turnover markers (BTMs), and microarchitecture with the use of dapagliflozin in type 2 diabetes mellitus (T2DM). Methods: Post-menopausal women (<65 years) with T2DM (both menopause and T2DM duration > 5 years and HbA1c 7-11%) were randomly allocated (1:1) to receive either add-on dapagliflozin with standard-of-care or standard-of-care alone for T2DM management. Those with osteoporosis, on anti—osteoporotic medication, chronic glucocorticoids (>3 months), thiazolidinediones, phenytoin, tamoxifen, estrogen, eGFR<30ml/min/1.73m2, contraindication/past usage of SGLT2i, or with known endocrinopathy were excluded. Patients were made Vitamin D sufficient [25(OH)D > 30ng/ml] with oral cholecalciferol (60K daily for 1 week), if deficient. BMD (DXA, Hologic), BTMs (P1NP, CTX) and microarchitecture were assessed at baseline, 6 and 12 months. Results: A total of 131 patients were screened, of which 101 were randomized (50 dapagliflozin, 51 non-dapagliflozin). The mean age (± SD) in the dapagliflozin group was 58.1 ± 5.8 years, diabetes duration was 9.4 ± 5.2 years and HbA1c was 8.5 ± 1.7%. Baseline clinico-biochemical, areal BMD, volumetric BMD, trabecular structural (number, thickness, separation) and cortical structural (thickness and porosity) parameters were comparable between both groups. Only cortical pore diameter (Ct.Po.Dm) (±SD) at radius (0.199 ± 0.04 vs 0.180 ± 0.03, p =0.01) and tibia (0.256 ± 0.04 vs 0.226 ± 0.03, p =0.001) were higher in the dapagliflozin than the non-dapagliflozin group. At 6 months, BMD at lumbar spine (LS), hip, femoral neck (FN), and distal radius and BTMs were comparable between the dapagliflozin (n=38) and the non-dapagliflozin (n=39) groups. However, there was significantly higher trabecular thickness (Tb.Th) (0.230 ± 0.02 vs 0.218 ± 0.01, p=0.003), cortical thickness (Co.Th) (1.104 ± 0.2 vs 0.998 ± 0.2, p=0.04), intra-cortical porosity (Ct.Po) (0.008 ± 0.005 vs 0.005 ± 0.003, p= 0.020) and Ct.Po.Dm (0.192 ± 0.03 vs 0.169 ± 0.02, p=0.003), all at radius in the dapagliflozin group. At 12 months follow-up, BMD (g/cm2) at all 4 sites were again comparable between the dapagliflozin (n=36) and non-dapagliflozin (n=36) groups. Serum CTX (pg/ml) (388.8 ± 191.5 vs 327.4 ± 140.8, p = 0.06), and P1NP (ng/ml) (38.8 ± 16.3 vs 32.5 ± 16.3, p = 0.12) were non-significantly higher with dapagliflozin use. Among microarchitecture parameters, only Ct.Po.Dm at the radius (0.189 ± 0.03 vs 0.169 ± 0.03, p= 0.025) and tibia (0.251 ± 0.05 vs 0.228 ± 0.03, p= 0.030) remained significantly higher in the dapagliflozin group. Conclusion: Dapagliflozin has no long-term detrimental effects on BMD, BTMs or bone microarchitecture after 1 year of treatment in postmenopausal women with T2DM. Presentation: 6/1/2024