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High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control

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Abstract

Summary

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.

Introduction

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.

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Abbreviations

T1D:

Type 1 diabetes

BMD:

Bone mineral density

HbA1c :

Glycated haemoglobin A1c

SD:

Standard deviation

AGEs:

Advanced glycation end products

CML:

N-ε-(carboxymethyl)-lysine

esRAGE:

Endogenous secretory receptor for AGEs

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Acknowledgments

The study was funded by a grant of Merck Pharma GmbH, Germany.

Conflicts of interest

Thomas Neumann, Sabine Lodes, Bettina Kästner, Sybille Franke, Michael Kiehntopf, Thomas Lehmann, Ulrich Alois Müller, Gunter Wolf and Alexander Sämann declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Internal Medicine III, Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany

    T. Neumann, S. Lodes, B. Kästner, S. Franke, U. A. Müller, G. Wolf & A. Sämann

  2. Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany

    M. Kiehntopf

  3. Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Jena, Germany

    T. Lehmann

Authors
  1. T. Neumann
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  2. S. Lodes
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  3. B. Kästner
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  4. S. Franke
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  5. M. Kiehntopf
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  6. T. Lehmann
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  7. U. A. Müller
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  8. G. Wolf
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  9. A. Sämann
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Corresponding author

Correspondence to T. Neumann.

Additional information

This study was conducted according to the Declaration of Helsinki.

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Neumann, T., Lodes, S., Kästner, B. et al. High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control. Osteoporos Int 25, 1527–1533 (2014). https://doi.org/10.1007/s00198-014-2631-7

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  • DOI: https://doi.org/10.1007/s00198-014-2631-7

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