title: High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control.
abstract: Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD.
  
  
  BACKGROUND
  Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength.
  
  
  METHODS
  In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated.
  
  
  RESULTS
  Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score -0.76 ± 0.94 vs. -0.23 ± 1.02; p = 0.031) and total hip (z-score -0.54 ± 0.93 vs. 0.11 ± 1.11; p = 0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1 ± 53.6 vs. 133.2 ± 40.4; p = 0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95% CI 1.00-1.03/pmol/ml increase of pentosidine; p = 0.008 and odds ratio 1.93, 95% CI 1.16-3.20 per percentage increase of HbA1c; p = 0.011).
  
  
  CONCLUSIONS
  The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.
authors.affiliation: Department of Internal Medicine III, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany, thomas.neumann@med.uni-jena.de.
authors.forename: T
authors.initials: T
authors.lastname: Neumann
authors.forename: S
authors.initials: S
authors.lastname: Lodes
authors.forename: B
authors.initials: B
authors.lastname: Kästner
authors.forename: S
authors.initials: S
authors.lastname: Franke
authors.forename: M
authors.initials: M
authors.lastname: Kiehntopf
authors.forename: T
authors.initials: T
authors.lastname: Lehmann
authors.forename: U A
authors.initials: UA
authors.lastname: Müller
authors.forename: G
authors.initials: G
authors.lastname: Wolf
authors.forename: A
authors.initials: A
authors.lastname: Sämann
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015519:Bone Density / Q000502:physiology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D018570:Risk Assessment / Q000379:methods
chemical_list: D001120:Arginine; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008239:Lysine; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C062187:pentosidine