DPP4 Activities Are Associated with Osteopenia/Osteoporosis and Fracture Risk in Newly Diagnosed Type 2 Diabetes

Abstract

Background. Recent studies have shown the beneficial effect of dipeptidyl peptidase-4 (DPP4) inhibitor on bone turnover in diabetes mellitus. However, little clinical evidence for DPP4 activity in newly diagnosed type 2 diabetes is available. This study was designed to investigate the relationship between plasma DPP4 activity and osteoporosis/osteopenia and fracture risk in newly diagnosed type 2 diabetes. Methods. A total of 147 subjects with newly diagnosed type 2 diabetes were enrolled for this cross-sectional study. The bone mineral density (BMD) at the lumbar spine (L1-4) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) was assessed by a modified fracture risk algorithm (FRAX) tool. The plasma DPP4 activity and clinical variables were measured. Correlation analyses between DPP4 activity and osteoporosis/osteopenia and fracture risk were performed. Results. Elevated plasma DPP activities were significantly associated with a higher proportion of osteoporosis/osteopenia (50% for quartile-1, 56.4% for quartile-2, 65.8% for quartile-3 and 72.2% for quartile-4). With increasing plasma DPP activities, the incidence rate of osteoporosis/osteopenia is gradually increasing ( P for the trend between quartiles = 0.04). Of note, a statistically significant linear correlation was found between plasma DPP4 activities and modified FRAX MOF (r = 0.20, P = 0.02 ). Moreover, plasma DPP4 activities were also positively related to modified FRAX HF in newly diagnosed type 2 diabetic patients (r = 0.21, P = 0.01 ). Conclusions. Elevated plasma DPP4 activity tended to be associated with a higher proportion of osteoporosis/osteopenia and increased the fracture risk in newly diagnosed type 2 diabetes.

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

“…A human study reported that elevated plasma DPP activities were associated with a higher proportion of osteoporosis/osteopenia in people with newly diagnosed T2D. (90) While not directly linked to DPP-4i use, this finding suggests a potential relationship between DPP activity and bone health in people with T2D. Elevated DPP activity may be an indicator of underlying mechanisms that could influence bone health, warranting further investigation.…”

Non-Specific Inhibition of Dipeptidyl Peptidases 8/9 by Dipeptidyl Peptidase 4 Inhibitors Negatively Affects Mesenchymal Stem Cell Differentiation

“…Furthermore, it has been found that in normoglycemic postmenopausal women, DPP4 activity is associated with an increased risk of osteoporosis, insulin resistance, inflammation and decreased GLP-1 levels [20]. In addition, high plasma DPP4 levels in type II diabetic patients have been linked with bone loss, as well as an increased risk of bone fractures [21].…”

The Multiple Biological Functions of Dipeptidyl Peptidase-4 in Bone Metabolism

“…However, a 13-year follow-up study ( 41 ) of 1,536 community-based elderly adults revealed that there was no significant association between basal DPP4 activity and hip BMD, lumbar spine BMD, or incidence of hip fractures. A cross-sectional study with 147 newly diagnosed T2D showed that elevated sDPP4 activity was positively associated with the risk of osteoporosis/osteopenia and fracture ( 42 ). However, a study ( 43 ) of 204 male Japanese diabetics showed no correlation between DPP4 levels and BMD in the lumbar spine or femoral neck.…”