Characteristics of bone strength and metabolism in type 2 diabetic model Tsumura, Suzuki, Obese Diabetes mice

Abstract

Objective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia, hyperinsulinemia, and complications such as obesity and osteoporosis. The Tsumura, Suzuki, Obese Diabetes (TSOD) mouse is an animal model of spontaneous obese T2DM. However, bone metabolism in TSOD mice is yet to be investigated. The objective of the present study was to investigate the effects of T2DM on bone mass, metabolism, microstructure, and strength in TSOD mice. Methods: We determined the following parameters in TSOD mice and Tsumura, Suzuki, Non-obesity (TSNO) mice (as controls): serum glucose levels; serum insulin levels; bone mass; bone microstructure; bone metabolic markers; and bone strength. We also performed the oral glucose tolerance test and examined histological sections of the femur. We compared these data between both groups at pre-diabetic (10 weeks) and established (20 weeks) diabetic conditions. Results: Bone strength, such as extrinsic mechanical properties, increased with age in the TSOD mice and intrinsic material properties decreased at both 10 weeks and 20 weeks. Bone resorption marker levels in TSOD mice were significantly higher than those in the control mice at both ages, but there was no significant difference in bone formation markers between the groups. Bone mass in TSOD mice was lower than that in controls at both ages. The trabecular bone volume at the femoral greater trochanter increased with age in the TSOD mice. The femoral mid-diaphysis in TSOD mice was more slender and thicker than that in TSNO mice at both ages. Conclusions: Bone mass of the femur was lower in TSOD mice than in TSNO mice because hyperinsulinemia during pre-diabetic and established diabetic conditions enhanced bone resorption due to high bone turnover. In addition, our data suggest that the bone mass of the femur was significantly reduced as a result of chronic hyperglycemia during established diabetic conditions in TSOD mice. We suggest that bone strength in the femur deteriorated due to the reduction of bone mass and because the femoral mid-diaphysis was more slender in TSOD mice. Keywords: Bone strength, Bone mass, Bone microstructure, Bone metabolism, Tsumura, Suzuki, Obese Diabetes mice, Type 2 diabetes mellitus