TY - JOUR
T1 - Circulating levels of carboxy-methyl-lysine (CML) are associated with hip fracture risk
T2 - 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
Y1 - 2014/5
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 (189ng/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.
AB - 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 (189ng/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.
KW - bone mineral density
KW - bone quality
KW - carboxy-methyl-lysine
KW - cardiovascular health study
KW - hip fracture risk
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U2 - 10.1002/jbmr.2123
DO - 10.1002/jbmr.2123
M3 - Article
C2 - 24877243
AN - SCOPUS:84899109327
SN - 0884-0431
VL - 29
SP - 1061
EP - 1066
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 5
ER -