Age-related effect on the concentration of collagen crosslinks in human osteonal and interstitial bone tissue

Nyman, Jeffry S.; Roy, Anuradha; Acuna, Rae L.; Gayle, Heather J.; Reyes, M.; Tyler, Jerrod H.; Dean, David D.; Wang, Xiaodu

doi:10.1016/j.bone.2006.06.026

Cited by 84 publications

(59 citation statements)

References 48 publications

(57 reference statements)

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“…Our results show that collagen in older interstitial tissue contains higher levels of PEN (p Ͻ 0.0001) and two enzymatic crosslinks (PYD, p Ͻ 0.001 and DPD, p Ͻ 0.001) than younger osteonal tissue. Although our data on PYD and DPD levels agree with the ones reported by others, our results on PEN levels are opposite (34) and suggest a link between accumulation of glycation-derived crosslinks and normal aging of generally healthy subjects. Conversely, osteonal tissue has higher amount of osteopontin and osteocalcin than interstitial tissue, and this has not been demonstrated before.…”

contrasting

confidence: 49%

Biochemical Characterization of Major Bone-Matrix Proteins Using Nanoscale-Size Bone Samples and Proteomics Methodology

Sroga

Karim

Colón

et al. 2011

Molecular & Cellular Proteomics

119

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There is growing evidence supporting the need for a broad scale investigation of the proteins and protein modifications in the organic matrix of bone and the use of these measures to predict fragility fractures. However, limitations in sample availability and high heterogeneity of bone tissue cause unique experimental and/or diagnostic problems. We addressed these by an innovative combination of laser capture microscopy with our newly developed liquid chromatography separation methods, followed by gel electrophoresis and mass spectrometry analysis. Our strategy allows indepth analysis of very limited amounts of bone material, and thus, can be important to medical sciences, biology, forensic, anthropology, and archaeology. The developed strategy permitted unprecedented biochemical analyses of bone-matrix proteins, including collagen modifications, using nearly nanoscale amounts of exceptionally homogenous bone tissue. Dissection of fully mineralized bone-tissue at such degree of homogeneity has not been achieved before. Application of our strategy established that: (1) collagen in older interstitial bone contains higher levels of an advanced glycation end product pentosidine then younger osteonal tissue, an observation contrary to the published data; (2) the levels of two enzymatic crosslinks (pyridinoline and deoxypiridinoline) were higher in osteonal than interstitial tissue and agreed with data reported by others; (3) younger osteonal bone has higher amount of osteopontin and osteocalcin then older interstitial bone and this has not been shown before. Taken together, these data show that the level of fluorescent crosslinks in collagen and the amount of two major noncollagenous bone matrix proteins differ at the level of osteonal and interstitial tissue. We propose that this may have important implications for bone remodeling processes and bone microdamage formation.

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contrasting

confidence: 49%

Biochemical Characterization of Major Bone-Matrix Proteins Using Nanoscale-Size Bone Samples and Proteomics Methodology

Sroga

Karim

Colón

et al. 2011

Molecular & Cellular Proteomics

119

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“…Whether or not these factors have a biomechanically relevant effect independent of bone mass will depend on characteristics of bone remodeling that we currently know little about, such as the number and size of remodeling events and how well remodeling cavities are targeted to mechanical stress/strain and microscopic tissue damage. Additionally there is growing evidence that aspects of collagen such as the concentration of naturally occurring nonenzymatic cross-links, can be modified by bone turnover and can influence the biomechanical performance of bone specimens [36,[61][62][63][64][65]. Unfortunately regression models accounting for these relationships in cancellous bone specimens are not available so the potential effect is not listed in Table 1.…”

Section: Discussionmentioning

confidence: 99%

How can bone turnover modify bone strength independent of bone mass?

Hernandez¹

2008

Bone

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The amount of bone turnover in the skeleton is has been identified as a predictor of fracture risk independent of areal bone mineral density (aBMD) and is increasingly cited as an explanation for discrepancies between areal bone mineral density and fracture risk. A number of mechanisms have been proposed to explain how bone turnover influences bone biomechanics, including regulation of tissue degree of mineralization, the disconnection or fenestration of individual trabeculae by remodeling cavities, and the ability of cavities formed during the remodeling process to act as stress risers. While these mechanisms can influence bone biomechanics, they also modify bone mass. If bone turnover is to explain any of the observed discrepancies between fracture risk and areal bone mineral density, however, it must not only modify bone strength but modify bone strength in excess of what would be expected from the associated change in bone mass. This article summarizes biomechanical studies of how tissue mineralization, trabecular disconnection and the presence of remodeling cavities might have an effect on cancellous bone strength independent of bone mass. Existing data support the idea that all of these factors may have a disproportionate effect on bone stiffness and/or strength, with the exception of average tissue degree of mineralization, which is unlikely to have an effect on bone strength that is independent of aBMD. Disproportionate effects of mineral content on bone biomechanics may instead come from variation in tissue degree of mineralization at the micro-structural level. The biomechanical explanation for the relationship between bone turnover and fracture incidence remains to be determined but must be examined not in terms of bone strength but in terms of bone strength relative to bone mass.

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“…outside the loading pins), and the concentration of pentosidine (PE, a marker of nonenzymatic crosslinks) was quantified for half of it following the protocol of Bank et al [35] for high performance liquid chromatography. The concentration was measured in moles of PE per moles of collagen in which collagen was measured on the other half by a colorimetric assay of hydroxyproline (described in a previous study [36]). From sequential mass measurements of dry and ashed bone, we quantified the mineral-to-collagen ratio (Min/Org) using a small piece of specimen from the other non-loaded region of each specimen.…”

Section: Compositional Analysismentioning

confidence: 99%

Measurements of mobile and bound water by nuclear magnetic resonance correlate with mechanical properties of bone

Nyman

Nicolella

et al. 2008

Bone

Self Cite

179

189

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Since clinical measures of bone mineral density do not necessarily predict whether a person will fracture a bone without an intervention, there is a need to find supplementary tools for assessing bone quality. Presently, we hypothesized that measures of mobile and bound water by a Nuclear Magnetic Resonance (NMR) technique are correlated with bone strength and toughness, respectively. To test this, bending specimens from the mid-diaphysis of 18 human femurs were collected from 18 male donors and divided into middle aged and elderly groups. After NMR measurements of each hydrated specimen, an inversion technique was used to convert the free induction decay data into a distribution of spin-spin (T2) relaxation rates. Then, the distribution resolved into three distinct components that likely represent solid hydrogen, water bound to bone tissue, and mobile water that occupy microscopic pores within the bone specimen. The integrated signal intensities of the bound and mobile components were normalized by the wet mass of the specimen. Following NMR measurements, three point bending tests were conducted to determine the modulus of elasticity, flexure strength, and work to fracture of each specimen. Next, the porosity, mineral-to-collagen ratio, and pentosidine concentration were measured. In this sample of human cortical bone, there was no age-related difference in the amount of mobile water, but the decrease in the amount of bound water with increasing age was statistically significant. Moreover, bound water was associated with both strength and work to fracture of bone, while mobile water was correlated with modulus of elasticity and appeared to quantify the level of microscopic pores within bone. On the other hand, bound water was correlated with the concentration of non-enzymatic collagen crosslinks. The results of this study indicate that quantifying mobile and bound water with magnetic resonance techniques could potentially serve as indicators of bone quality.

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Age-related effect on the concentration of collagen crosslinks in human osteonal and interstitial bone tissue

Cited by 84 publications

References 48 publications

Biochemical Characterization of Major Bone-Matrix Proteins Using Nanoscale-Size Bone Samples and Proteomics Methodology

Biochemical Characterization of Major Bone-Matrix Proteins Using Nanoscale-Size Bone Samples and Proteomics Methodology

How can bone turnover modify bone strength independent of bone mass?

Measurements of mobile and bound water by nuclear magnetic resonance correlate with mechanical properties of bone

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