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

    10 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

    Fingerprint

    Hospitalization
    Cohort Studies
    Prospective Studies
    Osteoporotic Fractures
    Pelvic Bones
    Calcaneus
    Hip Fractures
    Confidence Intervals
    Glomerular Filtration Rate
    Bone Density
    Lipocalin-2
    Bone and Bones
    Information Storage and Retrieval
    Information Systems
    Body Mass Index
    Homeostasis
    Exercise
    Kidney
    Genes

    Cite this

    @article{45ea57814df148caae886d808459c191,
    title = "Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study",
    abstract = "{\circledC} 2015 American Society for Bone and Mineral Research. {\circledC} 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.",
    author = "Wai Lim and G. Wong and E.M. Lim and E. Byrnes and Kun Zhu and A. Devine and Nathan Pavlos and Richard Prince and Joshua Lewis",
    year = "2015",
    month = "10",
    day = "19",
    doi = "10.1002/jbmr.2546",
    language = "English",
    volume = "30",
    pages = "2078--2085",
    journal = "Journal of Bone & Mineral Research",
    issn = "0884-0431",
    publisher = "John Wiley & Sons",
    number = "11",

    }

    Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study. / Lim, Wai; Wong, G.; Lim, E.M.; Byrnes, E.; Zhu, Kun; Devine, A.; Pavlos, Nathan; Prince, Richard; Lewis, Joshua.

    In: Journal of Bone and Mineral Research, Vol. 30, No. 11, 19.10.2015, p. 2078-2085.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study

    AU - Lim, Wai

    AU - Wong, G.

    AU - Lim, E.M.

    AU - Byrnes, E.

    AU - Zhu, Kun

    AU - Devine, A.

    AU - Pavlos, Nathan

    AU - Prince, Richard

    AU - Lewis, Joshua

    PY - 2015/10/19

    Y1 - 2015/10/19

    N2 - © 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.

    AB - © 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.

    U2 - 10.1002/jbmr.2546

    DO - 10.1002/jbmr.2546

    M3 - Article

    VL - 30

    SP - 2078

    EP - 2085

    JO - Journal of Bone & Mineral Research

    JF - Journal of Bone & Mineral Research

    SN - 0884-0431

    IS - 11

    ER -