Circulating Levels of Carboxy-Methyl-Lysine ( CML) Are Associated With Hip Fracture Risk: The Cardiovascular Health Study

被引:47
作者
Barzilay, Joshua I. [1 ,2 ]
Buzkova, Petra [3 ]
Zieman, Susan J. [4 ]
Kizer, Jorge R. [5 ]
Djousse, Luc [6 ,7 ]
Ix, Joachim H. [8 ]
Tracy, Russell P. [9 ,10 ]
Siscovick, David S. [11 ]
Cauley, Jane A. [12 ]
Mukamal, Kenneth J. [13 ]
机构
[1] Kaiser Permanente Georgia, Div Endocrinol, Atlanta, GA USA
[2] Emory Sch Med, Div Endocrinol, Atlanta, GA USA
[3] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[4] NIA, Geriatr Branch Off, NIH, Bethesda, MD 20892 USA
[5] Albert Einstein Coll Med, Dept Med, Div Epidemiol & Populat Hlth, Bronx, NY USA
[6] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Boston, MA USA
[8] Univ Calif San Diego, Div Nephrol, San Diego VA Healthcare Syst, San Diego, CA 92103 USA
[9] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA
[10] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA
[11] Univ Washington, Dept Med, Seattle, WA USA
[12] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA
[13] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA
关键词
CARBOXY-METHYL-LYSINE; HIP FRACTURE RISK; BONE QUALITY; CARDIOVASCULAR HEALTH STUDY; BONE MINERAL DENSITY; GLYCATION END-PRODUCTS; COLLAGEN CROSS-LINKS; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; PENTOSIDINE; SERUM; OSTEOPOROSIS; BONE;
D O I
10.1002/jbmr.2123
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (c) 2014 American Society for Bone and Mineral Research.
引用
收藏
页码:1061 / 1066
页数:6
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