SUN-587 Evaluation of DPP3 Activity as a Potential Marker of bone health in Type 2 Diabetes

Disclosure: A. Naciu: None. G. Tabacco: None. E. Silvi: None. C. Menale: None. M. Schiavone: None. T. Giovanna: None. A. Palermo: None. Background: The diagnosis of bone fragility in Type 2 Diabetes (T2D) is very challenging as patients have a high risk of fragility fractures despite normal or high bone mineral density (BMD). One of the main mechanisms that can explain the impairment of bone strength in T2D is the oxinflammation induced by chronic hyperglycemia. Dipeptidyl peptidase 3 (DPP3) is a ubiquitous zinc-dependent exopeptidase activating the Keap1-Nrf2 antioxidant pathway. We demonstrated that lack of DPP3 in the mouse model resulted in sustained oxidative stress and bone loss. We also demonstrated a significant reduction in serum Dpp3 activity in postmenopausal women with severe osteoporosis. We hypothesize that DPP3 may play a role in diabetic osteopathy. Aim: to evaluate DPP3 activity in T2D compared to age and sex-matched controls Methods: T2D post-menopausal women treated with metformin and age-matched post-menopausal women as control group. Subjects underwent fasting blood samples, Dual-energy x-ray absorptiometry at the lumbar spine (L1-L4), total hip (TH), femoral neck (TH), and nondominant radius and thoraco lumbar radiographs (T4-L4) for the evaluation of vertebral fractures. Results: This report includes 34 T2D subjects and 41 controls out of the 200 patients expected in the study. There were no differences in age, menopause age, calcium intake, serum calcium, phosphate, alkaline phosphatase, vitamin D and PTH levels between groups. T2D showed higher blood glucose and glycate hemoglobin compared to controls (glucose, mg/dL: 114,44 ± 23,09 vs 93,43 ± 10,7 p<0,001, HBA1c mmol/mol: 47,00 ± 4,0 vs 37,00 ± 2,0 p<0,001). T2D have higher BMD at all sites compared to controls: L1-L4 BMD 1,008 ± 0,181 vs 0,840 ± 0,113 p<0,001; FN BMD 0,737 ± 0,009 vs 0,607 ± 0,231 p< 0,001; TH BMD 0,882 ± 0,123 vs 0,774 ± 0,097 p<0,001 and distal radius BMD 0,624 ± 0,071 vs 0,575 ± 0,08 p= 0,007. There were no differences in the prevalence of VF between groups. There were no differences in TBS between groups (T2D: 1,295 ± 0,094 vs controls:1,302 ± 0,084 p= 0,749). Furthermore, there were no differences between groups in CTX, P1nP, Rank-L and OPG levels. T2D subjects showed lower Dpp3 activity compared to controls (DPP3 activity nmol 2-NA/mg/min 1,444 ±0,582 vs 1,716 ± 0,398 p= 0,038). Conclusions: These preliminary results indicate that DPP3 could be a potential marker of oxinflammation and diabetic osteopathy. Larger studies and preclinical evaluations are necessary to confirm these findings. Funding: GR-2021-12374645 Presentation: Sunday, July 13, 2025