PMID- 30866111 OWN - NLM STAT- MEDLINE DCOM- 20200813 LR - 20221207 IS - 1523-4681 (Electronic) IS - 0884-0431 (Print) IS - 0884-0431 (Linking) VI - 34 IP - 7 DP - 2019 Jul TI - Altered Tissue Composition, Microarchitecture, and Mechanical Performance in Cancellous Bone From Men With Type 2 Diabetes Mellitus. PG - 1191-1206 LID - 10.1002/jbmr.3711 [doi] AB - People with type 2 diabetes mellitus (T2DM) have normal-to-high BMDs, but, counterintuitively, have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of bone quality, including material properties or microarchitecture, that increase fragility independently of bone mass. Our objective was to elucidate the factors that influence fragility in T2DM by comparing the material properties, microarchitecture, and mechanical performance of cancellous bone in a clinical population of men with and without T2DM. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 31, age = 65 +/- 8 years, HbA1c = 7.1 +/- 0.9%; non-DM: n = 34, age = 62 +/- 9 years, HbA1c = 5.5 +/- 0.4%). The T2DM specimens had greater concentrations of the advanced glycation endproduct pentosidine (+ 36%, P < 0.05) and sugars bound to the collagen matrix (+ 42%, P < 0.05) than the non-DM specimens. The T2DM specimens trended toward a greater bone volume fraction (BV/TV) (+ 24%, NS, P = 0.13) and had greater mineral content (+ 7%, P < 0.05) than the non-DM specimens. Regression modeling of the mechanical outcomes revealed competing effects of T2DM on bone mechanical behavior. The trend of higher BV/TV values and the greater mineral content observed in the T2DM specimens increased strength, whereas the greater values of pentosidine in the T2DM group decreased postyield strain and toughness. The long-term medical management and presence of osteoarthritis in these patients may influence these outcomes. Nevertheless, our data indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix. These data suggest that high concentrations of advanced glycation endproducts can increase fragility by reducing the ability of bone to absorb energy before failure, especially for the subset of T2DM patients with low BV/TV. (c) 2019 American Society for Bone and Mineral Research. CI - (c) 2019 American Society for Bone and Mineral Research. FAU - Hunt, Heather B AU - Hunt HB AD - Department of Materials Science and Engineering, Cornell University, Ithaca, NY, USA. FAU - Torres, Ashley M AU - Torres AM AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA. FAU - Palomino, Pablo M AU - Palomino PM AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA. FAU - Marty, Eric AU - Marty E AD - Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA. FAU - Saiyed, Rehan AU - Saiyed R AD - Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA. FAU - Cohn, Matthew AU - Cohn M AD - Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA. FAU - Jo, Jonathan AU - Jo J AD - Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA. FAU - Warner, Stephen AU - Warner S AD - Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA. FAU - Sroga, Grazyna E AU - Sroga GE AUID- ORCID: 0000-0002-5158-1787 AD - Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. FAU - King, Karen B AU - King KB AD - Department of Orthopedics, University of Colorado School of Medicine, Aurora, CO, USA. AD - Surgical Service/Orthopaedic Service, Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, CO, USA. FAU - Lane, Joseph M AU - Lane JM AD - Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. FAU - Vashishth, Deepak AU - Vashishth D AD - Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. FAU - Hernandez, Christopher J AU - Hernandez CJ AUID- ORCID: 0000-0002-0712-6533 AD - Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA. AD - Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA. AD - Research Division, Hospital for Special Surgery, New York, NY, USA. FAU - Donnelly, Eve AU - Donnelly E AUID- ORCID: 0000-0001-8165-9568 AD - Department of Materials Science and Engineering, Cornell University, Ithaca, NY, USA. AD - Research Division, Hospital for Special Surgery, New York, NY, USA. LA - eng GR - DGE-1144153/Division of Graduate Education/International GR - W81XWH-15-1-0239/Congressionally Directed Medical Research Programs/International GR - R01AR057362/GF/NIH HHS/United States GR - K01AR064314/GF/NIH HHS/United States GR - Anne Dyde Laboratory Gift Fund/International GR - Cornell Colman Fellowship/Cornell University/International GR - R01 AR057362/AR/NIAMS NIH HHS/United States GR - R21 AR068061/AR/NIAMS NIH HHS/United States GR - R21AR068061/GF/NIH HHS/United States GR - K01 AR064314/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190517 PL - England TA - J Bone Miner Res JT - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JID - 8610640 RN - 0 (Glycated Hemoglobin A) RN - 0 (Glycation End Products, Advanced) SB - IM MH - Biomechanical Phenomena MH - Bone Density MH - Cancellous Bone/diagnostic imaging/*pathology/*physiopathology MH - Cohort Studies MH - Diabetes Mellitus, Type 2/diagnostic imaging/*physiopathology MH - Elastic Modulus MH - Glycated Hemoglobin/metabolism MH - Glycation End Products, Advanced/metabolism MH - Humans MH - Male MH - Middle Aged MH - Regression Analysis MH - Risk Factors MH - X-Ray Microtomography PMC - PMC6650336 MID - NIHMS1016984 OTO - NOTNLM OT - ADVANCED GLYCATION ENDPRODUCTS OT - CANCELLOUS BONE OT - COLLAGEN OT - DIABETES MELLITUS OT - FEMORAL NECK OT - FRACTURE OT - MECHANICAL PROPERTIES EDAT- 2019/03/14 06:00 MHDA- 2020/08/14 06:00 PMCR- 2020/07/01 CRDT- 2019/03/14 06:00 PHST- 2018/06/04 00:00 [received] PHST- 2019/01/24 00:00 [revised] PHST- 2019/02/19 00:00 [accepted] PHST- 2019/03/14 06:00 [pubmed] PHST- 2020/08/14 06:00 [medline] PHST- 2019/03/14 06:00 [entrez] PHST- 2020/07/01 00:00 [pmc-release] AID - 10.1002/jbmr.3711 [doi] PST - ppublish SO - J Bone Miner Res. 2019 Jul;34(7):1191-1206. doi: 10.1002/jbmr.3711. Epub 2019 May 17.