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Circulating levels of carboxy‐methyl‐lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study.
J Bone Miner Res 2014; 29(5):1061-6JB

Abstract

Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy‐methyl‐lysine (CML) are associated with risk of hip fracture.We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68–102 years; 39.8% male) for a median of 9.22 years (range, 0.01–12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD)measurement. There were 348 hip fractures during follow‐up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant‐years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27; 95% confidence interval [CI], 1.16–1.40]; p<0.001). Sequential adjustment for age, gender, race/ethnicity,body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95% CI, 1.05–1.31; p=0.006).In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures.

Authors

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Pub Type(s)

Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24877243

Citation

Barzilay, Joshua I., et al. "Circulating Levels of Carboxy‐methyl‐lysine (CML) Are Associated With Hip Fracture Risk: the Cardiovascular Health Study." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 29, no. 5, 2014, pp. 1061-6.
Barzilay JI, Bůžková P, Zieman SJ, et al. Circulating levels of carboxy‐methyl‐lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study. J Bone Miner Res. 2014;29(5):1061-6.
Barzilay, J. I., Bůžková, P., Zieman, S. J., Kizer, J. R., Djoussé, L., Ix, J. H., ... Mukamal, K. J. (2014). Circulating levels of carboxy‐methyl‐lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 29(5), pp. 1061-6.
Barzilay JI, et al. Circulating Levels of Carboxy‐methyl‐lysine (CML) Are Associated With Hip Fracture Risk: the Cardiovascular Health Study. J Bone Miner Res. 2014;29(5):1061-6. PubMed PMID: 24877243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating levels of carboxy‐methyl‐lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study. AU - Barzilay,Joshua I, AU - Bůžková,Petra, AU - Zieman,Susan J, AU - Kizer,Jorge R, AU - Djoussé,Luc, AU - Ix,Joachim H, AU - Tracy,Russell P, AU - Siscovick,David S, AU - Cauley,Jane A, AU - Mukamal,Kenneth J, PY - 2014/5/31/entrez PY - 2014/5/31/pubmed PY - 2014/12/15/medline SP - 1061 EP - 6 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 29 IS - 5 N2 - Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy‐methyl‐lysine (CML) are associated with risk of hip fracture.We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68–102 years; 39.8% male) for a median of 9.22 years (range, 0.01–12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD)measurement. There were 348 hip fractures during follow‐up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant‐years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27; 95% confidence interval [CI], 1.16–1.40]; p<0.001). Sequential adjustment for age, gender, race/ethnicity,body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95% CI, 1.05–1.31; p=0.006).In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/24877243/full_citation L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24877243/ DB - PRIME DP - Unbound Medicine ER -