Evidence map›Paper›PMID 35798196›Full record

ReviewBone2022

Causative or associative: A critical review of the role of advanced glycation end-products in bone fragility.

Thomas L Willett, Paul Voziyan, Jeffry S Nyman

Open access · greenAbstract readReview
In one paragraph

Review in Bone, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
6.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 55 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Article
  6. Pentosidine as a biomarker for bone fragility: Molecular mechanisms, clinical relevance, and detection strategies.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2026
    Review
  7. Review
  8. Article
  9. Interaction between diabetes and osteoporosis: imbalance between inflammation and bone remodeling.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Obese-diabetic femaleJBMR plus · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Thomas L WillettBiomedical Engineering Program, Systems Design Engineering, University of Waterloo, Waterloo, Ontario, Canada. Electronic address: thomas.willett@uwaterloo.ca.
Paul VoziyanDepartment of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jeffry S NymanDepartment of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA. Electronic address: jeffry.s.nyman@vumc.org.
Vanderbilt University Medical Center · USUniversity of Waterloo · CA

Funding

The Roles of Collagen and Water in the Fracture Resistance of BoneR01AR063157 · NIAMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NYMAN, JEFFRY STEPHEN · 2012 to 2025
$3.9M
Diabetes-Related Changes Affecting Bone QualityI01BX004297 · VA · VETERANS HEALTH ADMINISTRATION · PI NYMAN, JEFFRY STEPHEN · 2019 to 2023
–
BLRD VA I01 BX004297NIAMS NIH HHS R01 AR063157
6 · The paper itself

Abstract

The accumulation of advanced glycation end-products (AGEs) in the organic matrix of bone with aging and chronic disease such as diabetes is thought to increase fracture risk independently of bone mass. However, to date, there has not been a clinical trial to determine whether inhibiting the accumulation of AGEs is effective in preventing low-energy, fragility fractures. Moreover, unlike with cardiovascular or kidney disease, there are also no pre-clinical studies demonstrating that AGE inhibitors or breakers can prevent the age- or diabetes-related decrease in the ability of bone to resist fracture. In this review, we critically examine the case for a long-standing hypothesis that AGE accumulation in bone tissue degrades the toughening mechanisms by which bone resists fracture. Prior research into the role of AGEs in bone has primarily measured pentosidine, an AGE crosslink, or bulk fluorescence of hydrolysates of bone. While significant correlations exist between these measurements and mechanical properties of bone, multiple AGEs are both non-fluorescent and non-crosslinking. Since clinical studies are equivocal on whether circulating pentosidine is an indicator of elevated fracture risk, there needs to be a more complete understanding of the different types of AGEs including non-crosslinking adducts and multiple non-enzymatic crosslinks in bone extracellular matrix and their specific contributions to hindering fracture resistance (biophysical and biological). By doing so, effective strategies to target AGE accumulation in bone with minimal side effects could be investigated in pre-clinical and clinical studies that aim to prevent fragility fractures in conditions that bone mass is not the underlying culprit.

Indexed as

Diabetes MellitusFractures, BoneBone and BonesBone DensityGlycation End Products, AdvancedHumansGlycation End Products, AdvancedAdvanced glycation end-productAgingBiomarkersBone qualityCollagen type ICrosslinkingDiabetesMass spectrometryToughness

Identifiers

PMID35798196
PMCPMC10062699
OpenAlexW4283796350

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.