Serum non-esterified fatty acid levels and hip fracture risk: The Cardiovascular Health Study

Authors: BARZILAY, J - Kaiser Permanente; BUZKOVA, P - University Of Washington; DJOUSSE, LUC - Brigham & Women'S Hospital; IX, JOACHIM - University Of California; KIZER, JORGE - University Of California; CAULEY, JANE - University Of Pittsburgh; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MUKAMAL, KENNETH - Beth Israel Deaconess Medical Center

Submitted to: Osteoporosis International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/16/2021
Publication Date: 3/2/2021
Citation: Barzilay, J.I., Buzkova, P., Djousse, L., Ix, J.H., Kizer, J.R., Cauley, J.A., Matthan, N., Lichtenstein, A.H., Mukamal, K.J. 2021. Serum non-esterified fatty acid levels and hip fracture risk: The Cardiovascular Health Study. Osteoporosis International. https://doi.org/10.1007/s00198-021-05897-4.
DOI: https://doi.org/10.1007/s00198-021-05897-4

Interpretive Summary: Limited data suggests potential relations with fatty acid metabolism and bone health. Non-esterified fatty acids (NEFAs) are a group of fatty acids ranging in size and degree of saturation that circulate in blood unassociated with lipoprotein particles. Their main source is release from adipose (fat) tissue. Their association with hip fracture risk, common in older adults, has yet to be examined. Serum NEFA profiles were determined in Cardiovascular Health Study participants (n=2139, mean age 78 years) without known diabetes. Among the participants 303 incident hip fractures were documented during the 11 year follow up period. Higher total trans NEFA and the non-esterified long chain saturated fatty acid lignoceric acid (24:0) concentrations were associated with higher hip fracture risk. In contrast, higher non-esterified long chain saturated behenic acid (22:0) and long chain unsaturated fatty acid docosatetraenoic (22:4 n6) concentrations were associated with lower risk of hip fracture. These data suggest an unrecognized benefit of the systematic removal of trans fatty acids from the food supply.

Technical Abstract: Summary: Among elderly participants from the Cardiovascular Health Study, we found that non-esterified trans fatty acid levels had a significant prospective association with hip fracture risk. Other non-esterified fatty acid classes were not associated with hip fracture risk. Introduction: Serum non-esterified fatty acids (NEFAs) are bioactive metabolic intermediates that can be taken up by bone tissue. Their associations with hip fracture risk have not been previously examined. Methods: Thirty-five individual NEFAs in five classes (saturated [SFA], mono-un-saturated [MUFA], poly-unsaturated n-6 and n-3 [PUFA], and trans-FA) were measured in Cardiovascular Health Study participants (n = 2139, mean age 77.8 years) without known diabetes. The multivariable associations of NEFA levels with hip fracture risk were evaluated in Cox hazards models. Results: We documented 303 incident hip fractures during 11.1 years of follow-up. Among the five NEFA classes, total trans FA levels were positively associated with higher hip fracture risk (HR 1.17 [95% CI, 1.04, 1.31; p = 0.01] per one standard deviation higher level). The SFA lignoceric acid (24:0) was positively associated with higher risk (HR 1.09 [1.04, 1.1]; p < 0.001), while behenic (22:0) and docosatetraenoic (22:4 n6) acids were associated with lower risk (HR 0.76 [0.61, 0.94]; p = 0.01; 0.84 [0.70, 1.00]; p = 0.05, respectively). Conclusion: Total plasma trans NEFA levels are related to hip fracture risk, suggesting an unrecognized benefit of their systematic removal from food. Novel associations of individual NEFAs with hip fracture risk require confirmation in other cohort studies.