Bone histomorphometric and biomechanical analyses in Type 2 diabetic Goto-Kakizaki rats

Abstract

Objective To characterize the bone metabolism in Goto-Kakizaki(GK) rats,a spontaneous type 2 diabetic model.Methods Ten six-month old male GK rats were enrolled,with ten age-and sex-matched nondiabetic Wistar rats as controls.Blood samples were collected from the carotid artery for analysis of calcium,phosphate,osteocalcin and tartrate-resistant acid phosphatase activity.Bone mineral density was assessed by a dual energy X-ray absorptiometry at the femur and the fifth vertebral body,respectively,followed by biomechanical studies.The metaphyseal tibiae were embedded in methylmethacrylate to obtain undecalcified sections.Histomorphometric analysis was performed with an analysis software for multimedia pathological image.Results The body weight was much lower in the GK rats than that in the healthy Wistar rats(P0.01).Compared with the controls,the GK rats had significantly lower serum osteocalcin concentration [(4.97±0.49,6.75±0.71) μg/mL] and higher tartrate-resistant acid phosphatase activity [(17.92±5.23,8.31±2.69) U/L],both were P0.01.Bone density at the femur and lumbar vertebra was significantly deceased in the diabetic rats [(0.16±0.01,0.22±0.02;0.12±0.01,0.16±0.02) g/cm~2, P0.01].Bone morphologic analysis showed that the lengths of femur and lumbar were reduced by 10.3% and 9.5%,respectively,in the GK rats(P0.01),while no significant difference was seen in the values of cross-sectional area at both sites(P0.05).Histomorphometrical study showed significantly decreased trabecular bone volume,trabecular thickness,osteoid surface and thickness in GK rats [(15.72±1.18,19.13±1.13)%,(61.91± 4.54, 74.43 ± 3.63) μm,(18.18±1.25,19.63±1.07)%,(3.68±0.48,4.34±0.35) μm,P0.01 or 0.05],respectively.Further,the mineralizing surface,mineral apposition rate and bone formation rate were also decreased in the GK rats compared with those in the controls [(17.77±1.54,19.56±2.07)%,(1.07±0.22,1.35±0.16;0.20±0.03,0.26±0.04) μm/day,P0.05 or P0.01],along with an increase in mineralization lag time (2.66±0.56,2.12±0.35,P0.05).Conclusion Nonobese GK rats develop bone mass loss with increased risk of bone fracture.Type 2 diabetes mellitus per se may induce disequilibrium of bone remodelling by interfering with the function and activity of osteoblasts.