Key Findings
n3 fats may affect calcium absorption and excretion and modulate transcription factors involved in regulation of bone turnover and stem cell differentiation. Here, RBC ALA, EPA, and total n3 FAs were significantly inversely associated with risk of hip fracture. Conversely, women with an n6 to n3 FA ratio in the highest tertile had nearly twice the risk of hip fracture compared to those in the lowest tertile. In this nested case-control study within Womens Health Initiative, there was no significant relation of total RBC n6 FAs to hip fracture. This beneficial association was noted with either ALA or EPA, but not DHA. The results suggest a potential impact on skeletal health through increasing RBC ALA or EPA.
ABSTRACT
N3 and n6 polyunsaturated fatty acids (PUFA) in red blood cells (RBCs) are an objective indicator of PUFA status and may be related to hip fracture risk. The primary objective of this study was to examine RBC PUFAs as predictors of hip fracture risk in postmenopausal women. A nested case-control study (n of 400 pairs) was completed within the Womens Health Initiative (WHI) using 201 incident hip fracture cases from the Bone Mineral Density (BMD) cohort, along with 199 additional incident hip fracture cases randomly selected from the WHI Observational Study. Cases were matched on age, race, and hormone use with non–hip fracture controls. Stored baseline RBCs were analyzed for fatty acids using gas chromatography. After removing degraded samples, 324 matched pairs were included in statistical analyses. Stratified Cox proportional hazard models were constructed according to case-control pair status; risk of fracture was estimated for tertiles of RBC PUFA. In adjusted hazard models, lower hip fracture risk was associated with higher RBC alpha linolenic acid (tertile 3 [T3] hazard ratio [HR]: 0.44; 95 percent confidence interval [CI], 0.23–0.85; p for linear trend 0.0154), eicosapentaenoic acid (T3 HR: 0.46; 95percent CI, 0.24–0.87; p for linear trend 0.0181), and total n3 PUFAs (T3 HR: 0.55; 95percent CI, 0.30–1.01; p for linear trend 0.0492). Conversely, hip fracture nearly doubled with the highest RBC n6/n3 ratio (T3 HR: 1.96; 95 percent CI, 1.03–3.70; p for linear trend 0.0399). RBC PUFAs were not associated with BMD. RBC PUFAs were indicative of dietary intake of marine n3 PUFAs (Spearman’s rho of 0.45, p 0.0001), total n6 PUFAs (rho of 0.17, p 0.0001) and linoleic acid (rho of 0.09, p 0.05). These results suggest that higher RBC ALA, as well as eicosapentaenoic acid and total n3 PUFAs, may predict lower hip fracture risk. Contrastingly, a higher RBC n6/n3 ratio may predict higher hip fracture risk in postmenopausal women. (Authors abstract)
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