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Circulating levels of carboxy‐methyl‐lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study.

TitleCirculating levels of carboxy‐methyl‐lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2014
AuthorsBarzilay, JI, Bůzková, P, Zieman, SJ, Kizer, JR, Djoussé, L, Ix, JH, Tracy, RP, Siscovick, DS, Cauley, JA, Mukamal, KJ
JournalJ Bone Miner Res
Volume29
Issue5
Pagination1061-6
Date Published2014
ISSN1523-4681
KeywordsAge Factors, Aged, Female, Follow-Up Studies, Glycation End Products, Advanced, Hip Fractures, Humans, Incidence, Lysine, Male, Prospective Studies, Retrospective Studies, Risk Factors
Abstract<p>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 (189 ng/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.</p>
Alternate JournalJ. Bone Miner. Res.
PubMed ID24877243
PubMed Central IDPMC4523135
Grant ListN01HC55222 / HC / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL094555 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
HL094555 / HL / NHLBI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01 HC55222 / HC / NHLBI NIH HHS / United States