PMID- 36478472
OWN - NLM
STAT- MEDLINE
DCOM- 20230203
LR  - 20240202
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 38
IP  - 2
DP  - 2023 Feb
TI  - Increased Advanced Glycation Endproducts, Stiffness, and Hardness in Iliac Crest 
      Bone From Postmenopausal Women With Type 2 Diabetes Mellitus on Insulin.
PG  - 261-277
LID - 10.1002/jbmr.4757 [doi]
AB  - Individuals with type 2 diabetes mellitus (T2DM) have a greater risk of bone 
      fracture compared with those with normal glucose tolerance (NGT). In contrast, 
      individuals with impaired glucose tolerance (IGT) have a lower or similar risk of 
      fracture. Our objective was to understand how progressive glycemic derangement 
      affects advanced glycation endproduct (AGE) content, composition, and mechanical 
      properties of iliac bone from postmenopausal women with NGT (n = 35, 
      age = 65 +/- 7 years, HbA1c = 5.8% +/- 0.3%), IGT (n = 26, age = 64 +/- 5 years, 
      HbA1c = 6.0% +/- 0.4%), and T2DM on insulin (n = 25, age = 64 +/- 6 years, 
      HbA1c = 9.1% +/- 2.2%). AGEs were assessed in all samples using high-performance 
      liquid chromatography to measure pentosidine and in NGT/T2DM samples using 
      multiphoton microscopy to spatially resolve the density of fluorescent AGEs 
      (fAGEs). A subset of samples (n = 14 NGT, n = 14 T2DM) was analyzed with 
      nanoindentation and Raman microscopy. Bone tissue from the T2DM group had greater 
      concentrations of (i) pentosidine versus IGT (cortical +24%, p = 0.087; 
      trabecular +35%, p = 0.007) and versus NGT (cortical +40%, p = 0.003; trabecular 
      +35%, p = 0.004) and (ii) fAGE cross-link density versus NGT (cortical +71%, 
      p < 0.001; trabecular +44%, p < 0.001). Bone pentosidine content in the IGT group 
      was lower than in the T2DM group and did not differ from the NGT group, 
      indicating that the greater AGE content observed in T2DM occurs with progressive 
      diabetes. Individuals with T2DM on metformin had lower cortical bone pentosidine 
      compared with individuals not on metformin (-35%, p = 0.017). Cortical bone from 
      the T2DM group was stiffer (+9%, p = 0.021) and harder (+8%, p = 0.039) versus 
      the NGT group. Bone tissue AGEs, which embrittle bone, increased with worsening 
      glycemic control assessed by HbA1c (Pen: R(2)  = 0.28, p < 0.001; fAGE density: 
      R(2)  = 0.30, p < 0.001). These relationships suggest a potential mechanism by 
      which bone fragility may increase despite greater tissue stiffness and hardness 
      in individuals with T2DM; our results suggest that it occurs in the transition 
      from IGT to overt T2DM. (c) 2022 American Society for Bone and Mineral Research 
      (ASBMR).
CI  - (c) 2022 American Society for Bone and Mineral Research (ASBMR).
FAU - Lekkala, Sashank
AU  - Lekkala S
AUID- ORCID: 0000-0001-6638-9029
AD  - Department of Materials Science and Engineering, Cornell University, Ithaca, NY, 
      USA.
FAU - Sacher, Sara E
AU  - Sacher SE
AUID- ORCID: 0000-0001-8410-1500
AD  - Department of Materials Science and Engineering, Cornell University, Ithaca, NY, 
      USA.
FAU - Taylor, Erik A
AU  - Taylor EA
AD  - Sibley School of Mechanical and Aerospace Engineering Cornell University, Ithaca, 
      NY, USA.
FAU - Williams, Rebecca M
AU  - Williams RM
AD  - Meinig School of Biomedical Engineering Cornell University, Ithaca, NY, USA.
FAU - Moseley, Kendall F
AU  - Moseley KF
AD  - Division of Endocrinology, Johns Hopkins University School of Medicine, 
      Baltimore, MD, 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  - K01 AR064314/AR/NIAMS NIH HHS/United States
GR  - K23 DK093720/DK/NIDDK NIH HHS/United States
GR  - S10 OD018516/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221228
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 (Insulin)
RN  - 0 (Glycated Hemoglobin)
RN  - IY9XDZ35W2 (Glucose)
RN  - 9100L32L2N (Metformin)
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Humans
MH  - Female
MH  - Middle Aged
MH  - Aged
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Insulin
MH  - Glycated Hemoglobin
MH  - Ilium
MH  - Hardness
MH  - Postmenopause
MH  - *Glucose Intolerance
MH  - *Fractures, Bone
MH  - Glucose
MH  - *Metformin
MH  - Blood Glucose
PMC - PMC9898222
MID - NIHMS1855928
OTO - NOTNLM
OT  - bone
OT  - glycation
OT  - material properties
OT  - prediabetes
OT  - type 2 diabetes
EDAT- 2022/12/09 06:00
MHDA- 2023/02/04 06:00
PMCR- 2024/02/01
CRDT- 2022/12/08 13:03
PHST- 2022/11/25 00:00 [revised]
PHST- 2022/03/17 00:00 [received]
PHST- 2022/12/02 00:00 [accepted]
PHST- 2022/12/09 06:00 [pubmed]
PHST- 2023/02/04 06:00 [medline]
PHST- 2022/12/08 13:03 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - 10.1002/jbmr.4757 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2023 Feb;38(2):261-277. doi: 10.1002/jbmr.4757. Epub 2022 Dec 
      28.