A direct role of collagen glycation in bone fracture

Poundarik, Atharva A.
Wu, Ping-Cheng
Evis, Zafer
Sroga, Grazyna E.
Ural, Ani
Rubin, Mishaela
Vashishth, Deepak
Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone's organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen's ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000-5000;strain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk.


The effects of streptozotocin induced-diabetes on rat testes and the recovery role of vitamin c
Güldağ, Damla; Severcan, Feride; Department of Biology (2012)
Type I Diabetes is a multisystem disease having both biochemical and structural consequences. It causes alterations in carbohydrate, protein, and fat metabolisms due to hyperglycemia. Type I diabetes is also correlated with increased formation of free radicals and decreased levels of antioxidant potential. Lower endogeneous antioxidant amounts and elevated lipid peroxidation levels in diabetes constitute the basis of risk factors for the development of diabetic complications. These complications lead to irr...
Investigation of fluid structure interaction in cardiovascular system from diagnostic and pathological perspective
Salman, Hüseyin Enes; Yazıcıoğlu, Yiğit; Sert, Cüneyt; Department of Mechanical Engineering (2012)
Atherosclerosis is a disease of the cardiovascular system where a stenosis may develop in an artery which is an abnormal narrowing in the blood vessel that adversely affects the blood flow. Due to the constriction of the blood vessel, the flow is disturbed, forming a jet and recirculation downstream of the stenosis. Dynamic pressure fluctuations on the inner wall of the blood vessel leads to the vibration of the vessel structure and acoustic energy is propagated through the surrounding tissue that can be de...
Development of newborn galactosemia screening kits /
Ünal, Sıdıka Yağmur; Öktem, Hüseyin Avni; Yücel, Ayşe Meral; Department of Biotechnology (2015)
Galactosemia is an autosomal recessive disorder, caused by an impaired galactose metabolism, resulting in acute complications with high morbidity and mortality as soon as the infant begins a milk-based diet. Mutations in GALT, GALE and GLAK genes that are in the Leloir Pathway are responsible for the phenotype. Removing galactose from the diet is a critical, lifesaving intervention; yet this treatment does not prevent multiple long-term complications. Long-term neurological outcomes, particularly movement d...
Investigation of diabetes-induced effect on apex of rat heart myocardium by using cluster analysis and neural network approach: An FTIR study
Toyran, Neslihan; Severcan, Feride; Severcan, Mete; Turan, Belma (Hindawi Limited, 2007)
Diabetes mellitus (DM) is a progressive chronic disorder, which affects people belonging to all age groups of the population. This disease is accompanied by a greatly increased risk of cardiovascular death. In the present study, the effects of streptozotocin (STZ)-induced type 1 diabetes on apex myocardium of the rat heart have been investigated using Fourier Transform Infrared (FTIR) spectra. The cluster analysis has been applied to FTIR spectra to differentiate the diabetic samples from the normal control...
Regulation of Glutathione S-Transferase Mu with type 1 diabetes and its regulation with antioxidants
SADİ, GÖKHAN; Kartal, Deniz Irtem; Güray, Nülüfer Tülün (2013-01-01)
Objective: Increased oxidative stress is now related with the pathogenesis and the chronic complications associated with the disease, diabetes mellitus. While roles of oxidative stress in diabetic complications are widely studied, the molecular mechanisms playing role in the regulations of detoxification enzymes in the presence of antioxidants have not been clearly established because of the complexity of the pathways.
Citation Formats
A. A. Poundarik et al., “A direct role of collagen glycation in bone fracture,” JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, pp. 120–130, 2015, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/40533.