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Published: Nov 1, 2013
- A characteristic of biological aging is the non-enzymatic glycation of long-lasting proteins, such as collagen, which weakens collagen’s biomechanical properties and leads to increased bone matrix stiffening and fragility.
- This study shows that increasing levels of carboxy-methyl-lysine, an advanced glycation end product, are associated with hip fracture risk in older adults, independent of hip bone mineral density.
Patients with the highest level of serum carboxy-methyl-lysine were at the greatest risk for hip fracture, researchers found.
A higher quartile of carboxy-methyl-lysine in blood was significantly associated with increased risk of hip fracture, at 27% for each increase in quartile (95% CI 1.16-1.40, P<0.001), according to Joshua Barzilay, MD, of Kaiser Permanente of Georgia in Duluth, and colleagues.
This association remained significant after adjustment for age, sex, race, body mass index, smoking, alcohol consumption, prevalence coronary heart disease, energy expenditure, and estimated glomerular filtration rate (HR 1.17, 95% CI 1.05-1.31, P=0.006), they wrote in the Journal of Bone and Mineral Research.
Past research has shown vitamin D levels are predictive of hip fracture in older patients, and that aggressive osteoporosis care can lower rates of hip fracture. Additionally, bone strength has been associated with insulin resistance.
Carboxy-methyl-lysine is an advanced glycation end product, which can occur in the body in diabetes and with age. These end products can accumulate in bones and “leads to increased bone matrix stiffening and fragility,” they wrote.
They added that little past research has looked at bone fracture risk with presence of advanced glycation end products.
The authors analyzed serum carboxy-methyl-lysine levels in a cohort of 3,373 older patients enrolled in the Cardiovascular Health Study for associations with hip fracture risks.
All participants were Medicare-eligible U.S. citizens who received a baseline evaluation and annual follow-up from 1998 to 1999 and from 2005 to 2006. Researchers contacted participants by phone each year between the exam periods, and twice a year from 2000 to 2004 and again in 2007.
Participants’ renal function was measured through cystatin C levels, as was an estimation of glomerular filtration rate. They reported smoking history, medication use, history of falls in the year prior, kcal expenditure per week, and alcohol use through questionnaire and in-person interview.
In addition, measures of bone mineral density, weight, blood pressure, body mass index, grip strength, and time needed to walk 15 feet — in seconds — were recorded. Bone mineral density was recorded 1 to 2 years before the study.
Frailty was defined as having three or more of the following:
- Unintended weight loss of more than 10 pounds in the year prior
- Self-reported exhaustion “most of the time”
- Physical activity in the lowest 20% of the cohort (less than 383 kcal/week in men and less than 270 kcal/week in women)
- Grip strength in the lowest 20% of the cohort (less than 23 kg/m2 in men and less than 17 kg/m2 in women)
- Pace of walking in the lowest 20% of the cohort
Those with only one or two criteria were considered “pre-frail,” which meant the patient was at risk for frailty.
Hip fracture was recorded through patient report and confirmed through hospital records.
Carboxy-methyl-lysine was measured through assay blood analysis. Levels were divided into quartiles.
Median measure of carboxy-methyl-lysine was 584 ng/mL. Median follow-up was 9.22 years. There were 348 hip fractures over the follow-up period.
Participants with the lowest carboxy-methyl-lysine levels had the greatest survival free of hip fracture rates, with similar rates of fracture among the middle quartiles, and the highest rates of fracture among those in the highest quartile (log-rank P<0.001).
There was no significant differences between sexes or patients with or without diabetes for risks of hip fracture. There was also no significant association between carboxy-methyl-lysine levels and bone mineral density.
The authors said their study was limited by the limited characterization of bone health, such as absence of markers for bone turnover and resorption. Bone mineral density and carboxy-methyl-lysine were also only measured at a single point, and hemoglobin A1c and pentosidine were not measured.
The authors declared no conflicts of interest.
Primary source: Journal of Bone and Mineral Research
Source reference: Barzilay J, et al “Circulating levels of carboxy-methyl-lysine are associated with hip fracture risk: the cardiovascular health study” J Bone Miner Res 2013; DOI: 10.1002/jbmr.2123.
Cole Petrochko started his journalism career at MedPage Today in 2009, after graduating from New York University with B.A.s in Journalism and Psychology. When not writing for MedPage Today, he blogs about nerd culture, designs websites, and buys and sells collectible card game cards. He is based out of MedPage Today‘s Little Falls, N.J. Headquarters.
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