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

  • Joshua BarzilayEmail author
  • Petra BůžkováEmail author
  • Kenneth J. MukamalEmail author
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series (BDMDA)


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.


Hip fracture Bone quality Carboxymethyl-lysine (CML) Oxidative stress Advanced glycation end products (AGEs) 

List of Abbreviations


Advanced glycation end products


Bone mineral density


Body mass index




Cardiovascular Health Study


Confidence interval




Diabetes mellitus




Estimated glomerular filtration rate


Enzyme-linked immunosorbent assay


Hazard ratio


International Classification of Diseases


Interleukin 1


Interleukin 6




Nuclear factor kappa B


Receptor for advanced glycation end product


Tumor necrosis factor alpha


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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.Kaiser Permanente of GeorgiaDuluthUSA
  2. 2.Division of EndocrinologyEmory University School of MedicineAtlantaUSA
  3. 3.Department of BiostatisticsUniversity of WashingtonSeattleUSA
  4. 4.Department of General MedicineBeth Israel Deaconess Medical CenterBostonUSA

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