The Role Of AGEs In The Pathogenesis Of Diabetic Osteoporosis And The Mechanism Of Insulin Prevention

Objective: Diabetes is a risk factor for osteoporotic fractures. The causes of diabetic osteoporosis are diverse, and up to now isn't clear.But the interaction between AGE and RAGE is considered as an important way of diabetic osteoporosis. In diabetic patients' body, unusual increase of AGE is an important factor to diabetic osteoporosis. To explore the the role of AGEs in the pathogenesis of diabetic osteoporosis and the preventive effect of insulin on diabetic osteoporosis in streptozotocin (STZ)-diabetic rats in this experiment.Methods: 30 male Sprague-Dawley (SD) rats were randomized into control (C, n =10) and STZ-induced diabetic groups ( n = 20 ) , and then the diabetic rats wererandomized into 2 groups: Group A group ( n = 10) that was treated with insulinenough to control the high concentration of blood glucose strictly, and Group B group( n = 10) in which the high blood glucose was not controlled. 20 weeks later the animalswere sacrificed by bleeding. The serum levels of advanced glycosylation end products(AGEs) concentration was assessed by fluorescence spectrophotometry . Distractedtibiae and femora were analyzed radiographically and by DEXA. Contralateral tibiae wereanalyzed histologically. The presence of the receptor for advanced glycosylation end products(RAGE) in femora was evaluated by immunohistochemistry and RT-PCR.Results : After 20 weeks , in B group, AGEs in serum of diabetic rats increasesignificantly, while their BMD (bone mineral density ) cutdown significantly.Cortical bone of tibia and femur are very thin and are absorbed partly, and cavitas medullaris arewiden and bone texture of cancellated bone become rarefaction and thin. Viewing pathologicalsection of group B, bone trabecula become parce and thin,and cavitas medullaris enlarge.Bone trabecula disapear in some sectors. There are less bone trabecula in metaphysis of femur and there are more lipochondria in cavitas medullaris.OB of sur-bone-trabecula are rare. The expression levels of RAGE in groupe B was increased markedly and dyeing deeply. RT-PCR shows that the expression levels of RAGE in groupe B up-regulate. After insulin treatment, in group A, BMD (bone mineral density ) are normal. Morphous of bone trabecula recover, the mount of bone trabecula are more, paries of bone trabecula are thicker, cavitas medullaris don't enlarge significantly, and The expression levels of RAGE decrease. Compared with C group ,B group demonstrated obviously osteoporosis, the BMD (bone mineral density )values of femora was significantly reduced and the serum levels of AGEs was significantly increased(P<0. 01). The expression levels of RAGE in groupe B was increased markedly compared with group C(P<0. 01). Compared with B group ,A group did not demonstrated obviously osteoporosis, the BMD (bone mineral density )values of femora was significantly increased and the serum levels of AGEs was significantly reduced(P<0. 01). The expression levels of RAGE in groupe A was increased markedly compared with group B (P<0. 01).Conclusion :1. Diabetes can lead to cutting-down of BMD , increasing of AGE in serum , BS increasing, and body weight loss. Insulin treatment can improve all of above.2. Diabetes can lead to osteoporotic pathologic display of bone tissue of rats' tibia and femur, and insulin treatment can improve these display obviously.3. The expression levels of RAGE was increased markedly in diabetic rat' body , and insulin treatment can cut down the expression levels of RAGE.4. Diabetes can lead to osteoporosis, and insulin play some important roles in treatment and precaution of diabetic osteoporosis directly and indirectly.Above all, more AGEs is one of the important causative agents leading to diabetic osteoporosis of rat, and the effect of AGEs on bone is one of the important nosogenesises of diabetic osteoporosis. Insulin have some latent safety action on AGEs.