PMID- 29651097 OWN - NLM STAT- MEDLINE DCOM- 20191004 LR - 20191007 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Apr 12 TI - Unraveling the compromised biomechanical performance of type 2 diabetes- and Roux-en-Y gastric bypass bone by linking mechanical-structural and physico-chemical properties. PG - 5881 LID - 10.1038/s41598-018-24229-x [doi] LID - 5881 AB - Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with obesity and hyperglycemia. Roux-en-Y gastric bypass (RYGB) surgery is a common treatment for severely obese patients and T2DM. Both RYGB and T2DM are linked to increased skeletal fragility, though the exact mechanisms are poorly understood. Our aim was to characterize the structural, mechanical and compositional properties of bones from diet-induced obese and RYGB-treated obese (bypass) mice to elucidate which the exact factors are contributing to the increased skeletal fragility. To achieve this, a combinatory approach including microfocus X-ray computed tomography, 3-point bending, finite element modeling and Raman spectroscopy, was used. Compared to aged-matched lean controls, the obese mice displayed decreased cortical thickness, trabecular bone loss, decreased stiffness and increased Young's modulus. For the bypass mice, these alterations were even more pronounced, and additionally they showed low mineral-to-matrix ratio in the cortical endosteal area. Accumulation of the advanced glycation end-product (AGE) pentosidine was found in the cortex of obese and bypass groups and this accumulation was correlated with an increased Young's modulus. In conclusion, we found that the increased fracture risk in T2DM- and post-RYGB bones is mainly driven by accumulation of AGEs and macro-structural alterations, generating biomechanical dysfunctionality. FAU - Marin, Carlos AU - Marin C AD - Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. AD - Prometheus - Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium. AD - Biomaterials - BIOMAT, Department of Oral Health Sciences, KU Leuven, Leuven, Belgium. FAU - Papantonakis, Georgios AU - Papantonakis G AD - Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium. FAU - Sels, Kathleen AU - Sels K AD - Biomaterials - BIOMAT, Department of Oral Health Sciences, KU Leuven, Leuven, Belgium. FAU - van Lenthe, G Harry AU - van Lenthe GH AUID- ORCID: 0000-0001-8303-4959 AD - Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium. FAU - Falgayrac, Guillaume AU - Falgayrac G AUID- ORCID: 0000-0003-1806-1509 AD - Lille University, Littoral Cote d'Opale University, EA 4490, PMOI, Physiopathologie des Maladies Osseuses Inflammatoires, F-59000, Lille, France. FAU - Vangoitsenhoven, Roman AU - Vangoitsenhoven R AUID- ORCID: 0000-0003-3523-669X AD - Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. FAU - Van der Schueren, Bart AU - Van der Schueren B AD - Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. FAU - Penel, Guillaume AU - Penel G AD - Lille University, Littoral Cote d'Opale University, EA 4490, PMOI, Physiopathologie des Maladies Osseuses Inflammatoires, F-59000, Lille, France. FAU - Luyten, Frank AU - Luyten F AD - Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. AD - Prometheus - Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium. FAU - Vandamme, Katleen AU - Vandamme K AD - Prometheus - Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium. AD - Biomaterials - BIOMAT, Department of Oral Health Sciences, KU Leuven, Leuven, Belgium. FAU - Kerckhofs, Greet AU - Kerckhofs G AD - Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. greet.kerckhofs@uclouvain.be. AD - Prometheus - Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium. greet.kerckhofs@uclouvain.be. AD - Biomechanics lab, Institute of Mechanics, Materials, and Civil Engineering, UCLouvain, Louvain-la-Neuve, Belgium. greet.kerckhofs@uclouvain.be. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180412 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Glycation End Products, Advanced) RN - 94ZLA3W45F (Arginine) RN - BJ4I2X2CQJ (pentosidine) RN - K3Z4F929H6 (Lysine) SB - IM MH - Animals MH - Arginine/analogs & derivatives/metabolism MH - Biomechanical Phenomena MH - Bone and Bones/diagnostic imaging/metabolism/*physiopathology MH - Diabetes Mellitus, Type 2/diagnostic imaging/metabolism/physiopathology/*surgery MH - Female MH - Fractures, Bone/diagnostic imaging/metabolism/*physiopathology MH - Gastric Bypass/adverse effects MH - Glycation End Products, Advanced/*metabolism MH - Humans MH - Lysine/analogs & derivatives/metabolism MH - Male MH - Mice MH - Mice, Obese MH - Obesity/metabolism/pathology/*surgery MH - Skeleton/physiopathology MH - Tomography, X-Ray Computed MH - Weight Loss PMC - PMC5897570 COIS- The authors declare no competing interests. EDAT- 2018/04/14 06:00 MHDA- 2019/10/08 06:00 PMCR- 2018/04/12 CRDT- 2018/04/14 06:00 PHST- 2017/07/18 00:00 [received] PHST- 2018/03/06 00:00 [accepted] PHST- 2018/04/14 06:00 [entrez] PHST- 2018/04/14 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2018/04/12 00:00 [pmc-release] AID - 10.1038/s41598-018-24229-x [pii] AID - 24229 [pii] AID - 10.1038/s41598-018-24229-x [doi] PST - epublish SO - Sci Rep. 2018 Apr 12;8(1):5881. doi: 10.1038/s41598-018-24229-x.