Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study

Wai Lim, G. Wong, E.M. Lim, E. Byrnes, Kun Zhu, A. Devine, Nathan Pavlos, Richard Prince, Joshua Lewis

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research. Lipocalin 2 (LCN2) or neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a wide range of cells and pathological states. Mounting evidence suggests lipocalin 2 may be an important regulator of bone homeostasis. Recently it has been suggested LCN2 is a novel mechanoresponsive gene central to the pathological response to low mechanical force. We undertook a prospective study of 1009 elderly women over 70 years of age to study the association between circulating LCN2 and potential associated variables, including estimated glomerular filtration rate, physical activity, and baseline measures of hip bone density and heel bone quality. Osteoporotic fractures requiring hospitalizations were identified from the Western Australian Data Linkage System. Over 14.5 years, 272 (27%) of women sustained an osteoporotic fracture-related hospitalization; of these, 101 were hip fractures. Circulating LCN2 levels were correlated with body mass index and estimated glomerular filtration rate (r = 0.249, p <0.001 and r = -0.481, p <0.001, respectively) that modified the association with hip and heel bone measures. Per standard deviation increase in LCN2, there was a 30% multivariable-adjusted increase in the risk of any osteoporotic fracture (hazard ratio [HR] = 1.30, 95% confidence interval [CI] 1.13-1.50, p <0.001). In participants with elevated LCN2 levels above the median (76.6 ng/mL), there was an 80% to 81% increase in the risk of any osteoporotic or hip fracture (HR = 1.81, 95% CI 1.38-2.36, p <0.001 and HR = 1.80, 95% CI 1.16-2.78, p = 0.008, respectively). These associations remained significant after adjustment for total hip bone mineral density (p <0.05). In conclusion, we have demonstrated that circulating LCN2 levels predict future risk of osteoporotic fractures requiring hospitalization. Measurement of LCN2 levels may improve fracture prediction in addition to current fracture risk factors in the elderly, particularly in those with impaired renal function.
    Original languageEnglish
    Pages (from-to)2078-2085
    Number of pages8
    JournalJournal of Bone and Mineral Research
    Volume30
    Issue number11
    Early online date21 May 2015
    DOIs
    Publication statusPublished - 19 Oct 2015

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