title: DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats.
abstract: Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management.
authors: Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium; and.
authors: Lorenzo
authors: L
authors: Glorie
authors: Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium; and.
authors: Geert J
authors: GJ
authors: Behets
authors: Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
authors: Lesley
authors: L
authors: Baerts
authors: Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
authors: Ingrid
authors: I
authors: De Meester
authors: Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium; and patrick.dhaese@uantwerp.be.
authors: Patrick C
authors: PC
authors: D'Haese
authors: Laboratory of Pathophysiology, University of Antwerp, Antwerp, Belgium; and.
authors: Anja
authors: A
authors: Verhulst
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D019245:Compressive Strength / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D008297:Male; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000068900:Sitagliptin Phosphate; D013311:Streptozocin; D013314:Stress, Mechanical; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D013311:Streptozocin; D000068900:Sitagliptin Phosphate
keywords: diabetes; dipeptidyl peptidase IV; dipeptidyl peptidase IV inhibition; incretins; sitagliptin