Bone Abstracts

Dipeptidyl peptidase 4 (DPP4) modulates activity of proteins by removing two aminoterminal amino acids. DPP4 inhibitors are currently being used to improve glucose tolerance in type 2 diabetes patients by increasing the half-life of DPP4 substrates. It has been shown that these substrates do not only increase pancreatic insulin secretion, but also influence bone cell activity. The potential therapeutic effect of DPP4 inhibition on bone metabolism is thus worth being investigated. In the present study, we evaluated the effect of the DPP4 inhibitor sitagliptin (SG) on bone in the streptozotocin (STZ)-induced diabetic rat.

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 (2 g/l). Rats were scanned every 3 weeks using an in vivo micro-computed tomography scanner. After 6 and 12 weeks, rats were sacrificed after tetracyclin labeling for bone histomorphometric analysis of both static and dynamic bone parameters.

STZ-treated (diabetic) rats had significantly increased blood glucose compared to controls and reduced body weight, which was not influenced by SG. SG however significantly decreased diuresis and food consumption in diabetic rats. In vivo DPP4 inhibition of 89% was achieved in both SG-treated groups. Trabecular bone volume and bone over tissue volume ratio in the tibia was significantly lower in STZ-treated rats compared to untreated rats, but was normalized through SG treatment (significant in weeks 9 and 12). Trabecular thickness was decreased and trabecular spacing was increased in diabetic rats. SG treatment resulted in partial but significant recovery of trabecular parameters in diabetic rats. Cortical bone parameters and bone histomorphometry are currently assessed.

Results show an attenuation of diabetic bone loss through DPP4 inhibition. The effect of DPP4 inhibitor treatment on bone turnover is to be confirmed further through bone histomorphometric analysis.