Pentosidine as a Biomarker for Poor Bone Quality and Elevated Fracture Risk

Pritchard, Janet M.; Willett, Thomas L.

doi:10.1007/978-94-007-7693-7_32

Cited by 5 publications

(10 citation statements)

References 125 publications

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“…Pentosidine may also act as a marker for the formation of other AGE non‐enzymatic cross‐links. Note, however, that no other AGE cross‐links have been measured in bone nor their potential impact on bone biomechanics elucidated . In general, while a connection between pen concentration and mechanical properties is supported by our findings, more work is needed to elucidate the nature of these relationships.…”

Section: Discussionmentioning

confidence: 52%

“…In general, while a connection between pen concentration and mechanical properties is supported by our findings, more work is needed to elucidate the nature of these relationships. This is further motivated as while studies have shown a negative relationship between pen concentration and bone strength, other works have found a negative, positive, or no relationship between bone stiffness and pen concentration. The observed increase in pen levels and decrease in dpyr levels in the osteolytic vertebral bone seen in previous work may be indicative of diminished vertebral mechanical behavior independent of its compromised architecture.…”

Section: Discussionmentioning

confidence: 99%

“…However, pentosidine may act as an indicator for changes within the bone microenvironment which could impact bone mechanics. It has been suggested that pentosidine is a byproduct of, and hence a marker for, oxidative stress (net positive imbalance of reactive oxygen species) within the microenvironment . Oxidative stress may impact bone mechanics in a number of ways including: Reducing lysine based cross‐link concentration and collagen fragmentation/denaturing .…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that pentosidine is a byproduct of, and hence a marker for, oxidative stress (net positive imbalance of reactive oxygen species) within the microenvironment. 36 Oxidative stress may impact bone mechanics in a number of ways including: Reducing lysine based cross-link concentration 37,38 and collagen fragmentation/denaturing. 39,40 Both may lower bone toughness and mechanical behavior.…”

Section: Discussionmentioning

confidence: 99%

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Mechanical behavior of metastatic vertebrae are influenced by tissue architecture, mineral content, and organic feature alterations

Burke

Akens

Kiss

et al. 2018

Journal Orthopaedic Research

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Diminished vertebral mechanical behavior with metastatic involvement is typically attributed to modified architecture and trabecular bone content. Previous work has identified organic and mineral phase bone quality changes in the presence of metastases, yet limited work exists on the potential influence of such tissue level modifications on vertebral mechanical characteristics. This work seeks to determine correlations between features of bone (structural and tissue level) and mechanical behavior in metastatically involved vertebral bone. It is hypothesized that tissue level properties (mineral and organic) will improve these correlations beyond architectural properties and BMD alone. Twenty-four female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic (N = 8) or mixed (osteolytic/osteoblastic, N = 7) metastases, respectively. Twenty-one days post-inoculation L1-L3 pathologic vertebral motion segments were excised and μCT imaged. 3D morphometric parameters and axial rigidity of the L2 vertebrae were quantified. Sequential loading and μCT imaging measured progression of failure, stiffness and peak force. Relationships between mechanical testing (whole bone and tissue-level) and tissue-level material property modifications with metastatic involvement were evaluated utilizing linear regression models. Osteolytic involvement reduced vertebral trabecular bone volume, structure, CT-derived axial rigidity, stiffness and failure force compared to healthy controls (N = 9). Mixed metastases demonstrated similar trends. Previously assessed collagen cross-linking and proline-based residues were correlated to mechanical behavior and improved the predictive ability of the regression models. Similarly, collagen organization improved predictive regression models for metastatic bone hardness. This work highlights the importance of both bone content/architecture and organic tissue-level features in characterizing metastatic vertebral mechanics. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanical behavior of metastatic vertebrae are influenced by tissue architecture, mineral content, and organic feature alterations

Burke

Akens

Kiss

et al. 2018

Journal Orthopaedic Research

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“…AGEs are naturally fluorescent (e.g., PEN, crossline, pyrropyridine) or non-fluorescent (e.g., CML, GLU, PYR, GOLD and MOLD). Because PEN structure can withstand acid hydrolysis, it is a well-established measurement of AGE crosslinks in connective tissues along with the non-specific measurement of fluorescence of hydrolysates (5, 9).…”

Section: Introductionmentioning

confidence: 99%

Assessing glycation‐mediated changes in human cortical bone with Raman spectroscopy

Ünal

Uppuganti

Leverant

et al. 2018

Journal of Biophotonics

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Establishing a non-destructive method for spatially assessing advanced glycation end-products (AGEs) is a potentially useful step toward investigating the mechanistic role of AGEs in bone quality. To test the hypothesis that the shape of the amide I in the Raman spectroscopy (RS) analysis of bone matrix changes upon AGE accumulation, we incubated paired cadaveric cortical bone in ribose or glucose solutions and in control solutions for 4 and 16 weeks, respectively, at 37°C. Acquiring 10 spectra per bone with a 20X objective and a 830 nm laser, RS was sensitive to AGE accumulation (confirmed by biochemical measurements of pentosidine and fluorescent AGEs). Hyp/Pro ratio increased upon glycation using either 0.1 M ribose, 0.5 M ribose or 0.5 M glucose. Glycation also decreased the amide I sub-peak ratios (cm ) 1668/1638 and 1668/1610 when directly calculated using either second derivative spectrum or local maxima of difference spectrum, though the processing method (eg, averaged spectrum vs individual spectra) to minimize noise influenced detection of differences for the ribose-incubated bones. Glycation however did not affect these sub-peak ratios including the matrix maturity ratio (1668/1690) when calculated using indirect sub-band fitting. The amide I sub-peak ratios likely reflected changes in the collagen I structure.

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Advanced glycation endproducts and bone quality: practical implications for people with type 2 diabetes

Moseley

Sacher

et al. 2021

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review Individuals with type 2 diabetes (T2D) are at increased risk of fracture, often despite normal bone density. This observation suggests deficits in bone quality in the setting of abnormal glucose homeostasis. The goal of this article is to review recent developments in our understanding of how advanced glycation end products (AGEs) are incorporated into the skeleton with resultant deleterious effects on bone health and structural integrity in patients with T2D. Recent findings The adverse effects of skeletal AGE accumulation on bone remodeling and the ability of the bone to deform and absorb energy prior to fracture have been demonstrated both at the bench as well as in small human studies; however, questions remain as to how these findings might be better explored in large, population-based investigations. Summary Hyperglycemia drives systemic, circulating AGE formation with subsequent accumulation in the bone tissue. In those with T2D, studies suggest that AGEs diminish fracture resistance, though larger clinical studies are needed to better define the direct role of longstanding AGE accumulation on bone strength in humans as well as to motivate potential interventions to reverse or disrupt skeletal AGE deposition with the goal of fracture prevention.

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Pentosidine as a Biomarker for Poor Bone Quality and Elevated Fracture Risk

Cited by 5 publications

References 125 publications

Mechanical behavior of metastatic vertebrae are influenced by tissue architecture, mineral content, and organic feature alterations

Mechanical behavior of metastatic vertebrae are influenced by tissue architecture, mineral content, and organic feature alterations

Assessing glycation‐mediated changes in human cortical bone with Raman spectroscopy

Advanced glycation endproducts and bone quality: practical implications for people with type 2 diabetes

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