Effects Of Advanced Glycation End Products And Its Receptor In Type2Diabetes Mellitus Related Osteoporosis

Objective: Diabetic osteoporosis is a systemic, metabolic bone diseasecomplications of diabetes mellitus, characterize by the reduction of bone massin per unit volume, changes of bone microstructure, decreased bone strength,increased bone fragility and susceptibility to fracture. It can reduce bonestrength while increase fracture risk in the future. Previous studies found thatdiabetes induced osteopenia relates to many factors such as osmotic diuresiscaused by the high blood sugar that result in bone mineral metabolic disorderand calcium regulating hormone abnormalities, as well as insulin deficiencyweakens the osteogenic effect and insulin like growth factor generation. Inrecent years, many studies found that the interaction of advanced glycationend products (AGEs) and its receptor (receptor for advanced glycation endproducts, RAGE) play an important role in the development of diabeticosteoporosis. Pentosidine is one kind of AGEs, its content is positivelycorrelated related with the number of fluorescence AGEs, and a linearcorrelation between the plasma pentosidine concentrations and cortical bonepentosidine has been found. Thus, we predict that plasma pentosidine can bemarked as the total formation of AGEs. However, the effect of pentosidine andRAGE on type2diabetes mellitus related osteoporosis still exist manycontroversies. This study collected the clinical data of84cases of type2diabetes mellitus patients, and according to the diagnostic standard ofosteoporosis recommended by WHO, the subjects were divided into normalbone density group (DMN), diabetic osteopenia group (DMOPN) and diabeticosteoporosis group (DMOP). Plasma pentosidine, esRAGE, plasma type Ⅰcollagen carboxyl peptide (ICTP), typeⅠprecollagen N terminal propeptide(PINP) level and bone mineral density (BMD) was measured. We analyzed thecorrelation in pentosidine, esRAGE, their ratio, the clinical data, bone metabolism markers level and BMD. Furthermore, we evaluate the role ofplasma pentosidine and esRAGE in type2diabetes mellitus inducedosteoporosis, which will provide theory basis for their evaluation of bonemetabolism in type2diabetes mellitus related osteoporosis.Methods: A total of84type2diabetic inpatients were included in thesecond department of endocrine of the Third Hospital of Hebei MedicalUniversity from Jun.2013to Dec.2013, including42male and42female．Allsubjects’ BMD were measured at L2, L3, L4lumbar vertebrae，both femurs(neck, ward’s triangle, intertrochanter and total) by dual energy X rayabsorptiometry. According to the diagnostic standard of osteoporosisrecommended by WHO, the subjects were divided into DMN, DMOPN andDMOP group. Clinical parameters：gender, age, course of desease, pastmedical history, medicine history, height, weight, HbA1c, plasma PINP, ICTP,pentosidine, esRAGE were recorded, BMI index was calculated．Results:1Comparison of clinical data in DMN, DMOPN and DMOP groups.The course of disease in DMOP group was significantly longer thanDMN and DMOPN groups (P<0.01); the height of DMOP group wassignificantly lower than that of DMN and DMOPN group (P<0.01), gender,age, weight and BMI showed no difference between the three groups.2Comparison of pentosidine, esRAGE and esRAGE/pentosidine ratio inDMN, DMOPN and DMOP groups.There was a significant difference in pentosidine between DMN andDMOPN group (P<0.05), while the DMN and DMOP groups, DMOP andDMOP pentosidine have no significant difference; no significant differenceswas found in esRAGE and esRAGE/pentosidine ratio between the threegroups.3Comparison of bone metabolic markers in DMN, DMOPN and DMOPgroups.There was no significant difference of ICTP and PINP in DMN, DMOPNand DMOP group. 4Correlation analysis of pentosidine and esRAGE.Pentosidine was positively correlated with esRAGE (r=0.591, P<0.001).5Correlation analysis between pentosidine, esRAGE,esRAGE/pentosidine and clinical data.Pentosidine was positively correlated with BMI (r=0.22, P<0.05), whileno correlation was found in pentosidine with age, course of disease, height andbody weight; esRAGE and esRAGE/pentosidine ratio showed no obviouscorrelation with age, course of disease, height, weight and BMI.6Correlation analysis among pentosidine, esRAGE,esRAGE/pentosidine and bone metabolism markers and HbA1c.Pentosidine was positively correlated with ICTP (r=0.424, P<0.001);esRAGE/pentosidine was negatively correlated with ICTP (r=-0.75, P<0.001).No significant correlation was found between esRAGE and ICTP; PINP andHbA1c had no obvious correlation with pentosidine, esRAGE andesRAGE/pentosidine.7Correlation analysis of pentosidine, esRAGE, esRAGE/pentosidine andBMD at each site.Pentosidine, esRAGE and esRAGE/pentosidine had no obviouscorrelation with each site of BMD.Conclusions:1The course of disease in DMOP group was significantly longer thanDMN and DMOPN groups; the height of DMOP group was significantlylower than that of DMN and DMOPN group.2Pentosidine was positively correlated with esRAGE, BMI and ICTP;esRAGE/pentosidine was negatively correlated with ICTP.3There was a significant difference in pentosidine between DMN andDMOPN group. AGEs may interfer the process of bone remodeling byenhancing bone absorption, while not shown in the reduction of BMD.4Plasma pentosidine levels and esRAGE/pentosidine together with BMDand bone turnover markers may be a new choice of bone metabolismevaluation in diabetic related osteoporosis.