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Circulating Lipocalin 2 Levels Predict Fracture‐Related Hospitalizations in Elderly Women: A Prospective Cohort Study
Author(s) -
Lim Wai H,
Wong Germaine,
Lim Ee M,
Byrnes Elizabeth,
Zhu Kun,
Devine Amanda,
Pavlos Nathan J,
Prince Richard L,
Lewis Joshua R
Publication year - 2015
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2546
Subject(s) - medicine , hazard ratio , lipocalin , prospective cohort study , hip fracture , confidence interval , osteoporosis , renal function , cohort study , body mass index , bone remodeling , cohort
Abstract 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. © 2015 American Society for Bone and Mineral Research.