title: Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus.
abstract: Low-energy fractures are frequent complications in type 1 diabetes mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced glycation end products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and nonfracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and nonfracturing T1DM versus CTL. We analyzed iliac crest bone biopsies from 5 fracturing T1DM patients, 5 nonfracturing T1DM patients, and 5 healthy subjects, all age- and sex-matched. AGEs (pentosidine) in bone matrix was measured by high-performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Trabecular bone from fracturing T1DM exhibited significantly higher levels of pentosidine than CTL (p = 0.04) and was more mineralized than nonfracturing T1DM (p = 0.04) and CTL (p = 0.04). Trabecular bone was not significantly different in pentosidine between nonfracturing T1DM and CTL. Cortical bone from nonfracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and pentosidine (r' = 0.79, p < 0.003) and between HbA1c and DMB (r' = 0.64, p < 0.02). Both modifications could lead to less flexible bone (reduced modulus of elasticity) and a tendency toward low-energy fractures in T1DM patients.
authors.affiliation: INSERM, UMR 1033, Lyon, France.|Université de Lyon, Lyon, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Farlay
authors.affiliation: Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Laura A G
authors.initials: LA
authors.lastname: Armas
authors.affiliation: INSERM, UMR 1033, Lyon, France.|Université de Lyon, Lyon, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gineyts
authors.affiliation: Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Mohammed P
authors.initials: MP
authors.lastname: Akhter
authors.affiliation: Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, NE, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.affiliation: INSERM, UMR 1033, Lyon, France.|Université de Lyon, Lyon, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000328:Adult; D015519:Bone Density; D002113:Calcification, Physiologic; D048909:Diabetes Complications / Q000000981:diagnostic imaging / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography
chemical_list: D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; C517652:hemoglobin A1c protein, human
keywords: BONE QUALITY; FRACTURE; MINERALIZATION; PENTOSIDINE; TYPE 1 DIABETES MELLITUS