Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in Elderly Women: A Prospective Cohort Study.
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.
University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia.|Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Wai H
WH
Lim
Centre for Kidney Research, Children's Hospital at Westmead School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
Germaine
G
Wong
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia.|PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Ee M
EM
Lim
PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Elizabeth
E
Byrnes
University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia.|PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Kun
K
Zhu
School of Exercise and Health Sciences, Edith Cowan University, Joondalup, Australia.
Amanda
A
Devine
School of Surgery, Centre for Orthopaedic Research, University of Western Australia, Perth, Australia.
Nathan J
NJ
Pavlos
University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia.|PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Richard L
RL
Prince
University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia.|PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Joshua R
JR
Lewis
D000058:Accidental Falls; D000209:Acute-Phase Proteins; D000368:Aged; D015992:Body Mass Index; D015519:Bone Density; D005260:Female; D005919:Glomerular Filtration Rate; D006365:Heel / Q000000981:diagnostic imaging; D006620:Hip Fractures / Q000150:complications; D006760:Hospitalization; D006801:Humans; D016014:Linear Models; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D009043:Motor Activity; D058866:Osteoporotic Fractures / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012307:Risk Factors; D014463:Ultrasonography
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
ELDERLY WOMEN; FRACTURE RISK; LCN2; NGAL; OSTEOPOROSIS; PHYSICAL ACTIVITY