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Hip Fracture Risk Is Strongly Related to Circulating Levels of the Advanced Glycation End Product Carboxy-Methyl Lysine (CML)

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Biomarkers in Bone Disease

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Abstract

Advanced glycation end products (AGEs) are markers of oxidative stress, the process whereby the body is unable to neutralize the effects of oxygen radicals generated during the process of metabolism. Oxidative stress is believed to underlie (in part) the biological process of aging. In this chapter we describe how one particular AGE – carboxymethyl-lysine (CML) – is related to hip fracture risk in a cohort of over 3,000 older adults (mean age 78 years). Hip fractures are an age-related disorder with a high degree of morbidity and mortality and are costly to national health care systems.

The study found that for every one standard deviation increase in serum CML level the hazard ratio for hip fracture increased 27% (HR 1.27, 95% CI 1.16–1.40; p < 0.001). With adjustment for risk factors strongly associated with osteoporotic fractures (advanced age, low body mass index, white or Asian race, and low bone mineral density), as well as other factors (such as kidney function, alcohol use, and energy consumption), the risk remained significant (HR 1.17, 95% CI 1.05–1.31; p = 0.006).

It is concluded that serum CML levels are strongly associated with hip fracture risk independent of other risk factors for hip fracture. These findings suggest that serum CML levels may be a useful tool for gauging hip fracture risk.

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Abbreviations

AGEs:

Advanced glycation end products

BMD:

Bone mineral density

BMI:

Body mass index

CEL:

Nε-carboxyethyl-lysine

CHS:

Cardiovascular Health Study

CI:

Confidence interval

CML:

Carboxymethyl-lysine

DM:

Diabetes mellitus

DXA:

DEXA

eGFR:

Estimated glomerular filtration rate

ELISA:

Enzyme-linked immunosorbent assay

HR:

Hazard ratio

ICD-9:

International Classification of Diseases

IL1:

Interleukin 1

IL6:

Interleukin 6

IQ:

Interquartile

NF kB:

Nuclear factor kappa B

RAGE:

Receptor for advanced glycation end product

TNF-alpha:

Tumor necrosis factor alpha

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Author information

Authors and Affiliations

  1. Kaiser Permanente of Georgia, 3650 Steve Reynolds Blvd, Duluth, GA, 30096, USA

    Joshua Barzilay

  2. Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, USA

    Joshua Barzilay

  3. Department of Biostatistics, University of Washington, Building 29, Suite 210, 6200 NE 74th Street, Seattle, WA, 98115, USA

    Petra Bůžková

  4. Department of General Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA

    Kenneth J. Mukamal

Authors
  1. Joshua Barzilay
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  2. Petra Bůžková
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  3. Kenneth J. Mukamal
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Corresponding authors

Correspondence to Joshua Barzilay , Petra Bůžková or Kenneth J. Mukamal .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Department of Nutrition and Dietetics, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

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Barzilay, J., Bůžková, P., Mukamal, K.J. (2017). Hip Fracture Risk Is Strongly Related to Circulating Levels of the Advanced Glycation End Product Carboxy-Methyl Lysine (CML). In: Patel, V., Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7693-7_14

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