The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone

Abar, Orchid; Dharmar, S.; Tang, S. Y.

doi:10.1302/2046-3758.71.bjr-2017-0135.r1

Cited by 22 publications

(15 citation statements)

References 38 publications

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“…Although pyridoxamine is a known inhibitor of AGEs, namely when glucose causes AGE accumulation, we did not investigate whether a higher concentration of pyridoxamine (>50 mM) could prevent the ribose‐related decrease in bound water fraction over 4 weeks. A lower concentration of pyridoxamine (0.1 mM) was found to reduce the accumulation of fluorescent AGEs when human cortical bone was incubated in 0.1 M glucose for 7 days at 50°C . Because ribose is significantly more reactive than glucose and formation of ribose‐protein adducts (ie, AGE precursors) may be sufficient to affect bound water, it is possible that the PM concentration used in our study was not high enough to completely block the Maillard reaction between sugar and protein.…”

Section: Discussionmentioning

confidence: 84%

“…A lower concentration of pyridoxamine (0.1 mM) was found to reduce the accumulation of fluorescent AGEs when human cortical bone was incubated in 0.1 M glucose for 7 days at 50°C. (43) Because ribose is significantly more reactive than glucose and formation of ribose-protein adducts (ie, AGE precursors) may be sufficient to affect bound water, it is possible that the PM concentration used in our study was not high enough to completely block the Maillard reaction between sugar and protein. Lastly, there are inherent limitations in the use of cadaver bone as donor information is limited.…”

Section: Discussionmentioning

confidence: 95%

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Manipulating the Amount and Structure of the Organic Matrix Affects the Water Compartments of Human Cortical Bone

et al. 2019

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Being predictors of the mechanical properties of human cortical bone, bound and pore water measurements by magnetic resonance (MR) imaging are being developed for the clinical assessment of fracture risk. While pore water is a surrogate of cortical bone porosity, the determinants of bound water are unknown. Manipulation of organic matrix properties by oxidative deproteinization, thermal denaturation, or nonenzymatic glycation lowers bone toughness. Because bound water contributes to bone toughness, we hypothesized that each of these matrix manipulations affect bound water fraction (V bw /V bone ). Immersing cadaveric bone samples in sodium hypochlorite (NaClO) for 96 hours did not affect tissue mineral density or cortical porosity, but rather decreased V bw /V bone and increased short‐T 2 pore water signals as determined by 1 H nuclear MR relaxometry ( 1 H NMR). Moreover, the post treatment V bw /V bone linearly correlated with the remaining weight fraction of the organic matrix. Heating bone samples at 110°C, 120°C, 130°C, and then 140°C (∼24 hours per temperature and rehydration for ∼24 hours before 1 H NMR analysis) did not affect V bw /V bone . After subsequently heating them at 200°C, V bw /V bone increased. Boiling bone samples followed by heating at 110°C, 120°C, and then 130°C in water under pressure (8 hours per temperature) had a similar effect on V bw /V bone . Raman spectroscopy analysis confirmed that the increase in V bw /V bone coincided with an increase in an Amide I subpeak ratio that is sensitive to changes in the helical structure of collagen I. Glycation of bone by ribose for 4 weeks, but not in glucose for 16 weeks, decreased V bw /V bone , although the effect was less pronounced than that of oxidative deproteinization or thermal denaturation. We propose that MR measurements of bound water reflect the amount of bone organic matrix and can be modulated by collagen I helicity and by sugar‐derived post translational modifications of the matrix. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 95%

Manipulating the Amount and Structure of the Organic Matrix Affects the Water Compartments of Human Cortical Bone

et al. 2019

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“…One study found that IDI was correlated with femoral neck strength IDI (r = −0.478), and utilizing aBMD and IDI together in a multivariate model significantly increased the predictive ability of bone strength (r = 0.883) than either measurement alone 51 . BioDent was also capable of monitoring the effects of in vitro aminoguanidine and pyridoxamine incubation on ex vivo bone tissue mechanical behavior 52 . In another application, IDI was used to predict maximum screw torque in fracture fixation 53 .…”

Section: Biodent Studiesmentioning

confidence: 99%

Clinical Measurements of Bone Tissue Mechanical Behavior Using Reference Point Indentation

Chang

Easson

Tang

2018

Clinic Rev Bone Miner Metab

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Over the last thirty years, it has become increasingly clear the amount of bone (e.g. ‘bone quantity’) and the quality of the bone matrix (e.g. ‘bone quality’) both critically contribute to bone’s tissue-level mechanical behavior and the subsequent ability of bone to resist fracture. Although determining the tissue-level mechanical behavior of bone through mechanical testing is relatively straightforward in the laboratory, the destructive nature of such testing is unfeasible in humans and in animal models requiring longitudinal observation. Therefore, surrogate measurements are necessary for quantifying tissue-level mechanical behavior for the pre-clinical and clinical evaluation of bone strength and fracture risk in vivo. A specific implementation of indentation known as reference point indentation (RPI) enables the mechanical testing of bone tissue without the need to excise and prepare the bone surface. However, this compromises the ability to carefully control the specimen geometry that is required to define the bone tissue material properties. Yet the versatility of such measurements in clinical populations is provocative, and to date there are a number of promising studies that have utilized this tool to discern bone pathologies and to monitor the effects of therapeutics on bone quality. Concurrently, on-going efforts continue to investigate the aspects of bone material behavior measured by RPI, and the compositional factors that contribute to these measurements. There are currently two variants, cyclic- and impact- RPI, that have been utilized in pre-clinical and clinical studies. This review surveys clinical studies that utilize RPI, with particular emphasis on the clinical instrument, as well as the endeavors to understand the fundamental mechanisms of such measurements. Ultimately, an improved awareness in the tradeoffs and limitations of in vivo RPI is critical towards the effective and successful utilization of this tool for the overall improvement of fragility determination in the clinic.

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“…Moreover, studies using diabetic animals suggest that increased AGEs are associated with lower bone stiffness and are more susceptible to microcrack propagation compared with non‐diabetic controls, but there is little information regarding crack initiation and propagation due to AGEs in human bone . Further, about 12 studies in human bone focused on studying the effect of non‐enzymatic glycation on cancellous bone mechanical behavior, but only six studies report findings on cortical bone, two of which utilize bovine bone . There is some indication that in diabetes (where AGEs are particularly relevant) cortical bone is the primary bone type affected with a reduced quality .…”

mentioning

confidence: 99%

“…Another study illustrated that an increase in AGEs in human bone was associated with deteriorated reference point indentation properties but not with mechanical properties assessed by 3‐point bending tests . The last study illustrated that certain drug targets can be used to decrease AGEs in human bone with a consequent improvement in cyclic reference point indentation properties . In addition, there are drastic differences in AGE levels across these studies, which makes it even more difficult to compare the findings.…”

mentioning

confidence: 99%

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

Merlo

Aaronson

Vaidya

et al. 2019

Journal Orthopaedic Research

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Advanced glycation end-products (AGEs) have been suggested to contribute to bone fragility in type 2 diabetes (T2D). AGEs can be induced through in vitro sugar incubations but there is limited data on the effect of total fluorescent AGEs on mechanical properties of human cortical bone, which may have altered characteristics in T2D. Thus, to examine the effect of AGEs on bone directly in T2D patients with uncontrolled sugar levels, it is essential to first understand the fundamental mechanisms by studying the effects of controlled in vitro-induced AGEs on cortical bone mechanical behavior. Here, human cortical bone specimens from female cadaveric tibias (ages 57-87) were incubated in an in vitro 0.6 M ribose or vehicle solution (n = 20/group) for 10 days at 37°C, their mechanical properties were assessed by microindentation and fracture toughness tests, and induced AGE levels were quantified through a fluorometric assay. Results indicated that ribose-incubated bone had significantly more AGEs (+81%, p ≤ 0.005), lower elastic modulus assessed by traditional microindentation, and lower fracture toughness compared with vehicle controls. Furthermore, based on pooled data, increased AGEs were significantly correlated with deteriorated mechanical properties. The findings presented here show that the accumulation of AGEs allows for lower stiffness and increased ability to initiate a crack in human cortical bone. Statement of clinical significance: High sugar levels as in T2D results in deteriorated bone quality via AGE accumulation with a consequent weakening in bone's mechanical integrity.

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The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone

Cited by 22 publications

References 38 publications

Manipulating the Amount and Structure of the Organic Matrix Affects the Water Compartments of Human Cortical Bone

Manipulating the Amount and Structure of the Organic Matrix Affects the Water Compartments of Human Cortical Bone

Clinical Measurements of Bone Tissue Mechanical Behavior Using Reference Point Indentation

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

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