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advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean\u2009\u00b1\u2009standard deviation (SD) age was 73.7\u2009\u00b1\u20092.8 and 73.6\u2009\u00b1\u20092.9\u2009years in T2D (n\u00a0=\u00a0712) and non-diabetes (n\u00a0=\u00a02332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893\u2009\u00b1\u2009332 versus 771\u2009\u00b1\u2009270\u2009ng\/mL, p\u2009&amp;lt;\u20090.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24\u20131.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94\u20131.13; p for interaction\u00a0=\u00a00.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4466","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T03:38:13Z","timestamp":1637897893000},"page":"265-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4179-4006","authenticated-orcid":false,"given":"Ruban","family":"Dhaliwal","sequence":"first","affiliation":[{"name":"Metabolic Bone Disease Center State University of New York Upstate Medical University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-828X","authenticated-orcid":false,"given":"Susan K.","family":"Ewing","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Vashishth","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Semba","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann V.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA 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