Sitagliptin Alters Bone Composition in High-Fat-Fed Mice

Area of Science:

• Endocrinology
• Bone Biology
• Pharmacology

Background:

• Type 2 diabetes mellitus (T2DM) is a significant risk factor for bone fragility.
• Dipeptidyl peptidase-4 inhibitors (DPP4i) may reduce fracture risk, but the underlying mechanisms are unclear.

Purpose of the Study:

• To investigate the effects of sitagliptin on bone tissue strength and composition in a high-fat-fed mouse model of T2DM.
• To elucidate the impact of DPP4 inhibition on bone physiology.

Main Methods:

• Male NIH swiss mice were fed a high-fat diet for 150 days to induce T2DM.
• Sitagliptin or saline was administered for 3 weeks.
• Bone strength was assessed using three-point bending and nanoindentation.
• Bone microarchitecture was analyzed by microcomputed tomography.
• Bone composition was evaluated using Fourier transform infrared imaging and quantitative backscattered electron imaging.

Main Results:

• Sitagliptin treatment improved insulin sensitivity, glucose tolerance, and non-fasting insulin levels.
• Significant improvements in bone strength at both organ and tissue levels were observed.
• No alterations in trabecular or cortical bone microarchitecture were detected.
• Sitagliptin increased Ca mean, Ca turn, collagen maturity, mineral/matrix ratio, mineral maturity, and crystal size index.
• Bone strength improvements correlated significantly with changes in bone compositional parameters.

Conclusions:

• Sitagliptin enhances bone strength in a T2DM mouse model by improving bone compositional properties, not microarchitecture.
• These findings provide novel insights into the bone-protective mechanisms of DPP4 inhibitors.
• Sitagliptin demonstrates a potential benefit for bone health in the context of type 2 diabetes.