Associations between essential fatty acids, fish, and bone health in older adults: The Framingham Osteoporosis Study

N-3 and n-6 fatty acids are hypothesized to influence bone health through opposing effects, which regulate inflammatory cytokine production in cyclooxygenase (COX) and lipoxygenase (LOX) pathways. These cytokines are thought to modulate osteoclast activity. However, n-3 and n-6 fatty acids may exert effects through alternative pathways, including peroxisome proliferator-activator receptor (PPAR), nuclear factor kappa-beta (NF-kappaB), and lipid mediators that resolve inflammation.;We first examined associations among dietary essential fatty acids and fish intakes with cross-sectional (n=854) hip bone mineral density (BMD) at exam 20 (1988-89) and longitudinal (n=623) 4-y change in hip BMD among participants (mean ∼75 y) in the Framingham Osteoporosis Study. Significant interactions between AA and EPA+DHA intakes were observed cross-sectionally in women ( P = 0.03), and longitudinally in men (P < 0.01). Women in the highest quartile of both EPA+DHA and AA had the highest baseline FN-BMD (P-trend = 0.03 -- 0.06). Protective effects of AA were dependent on EPA+DHA intake. The highest intake of AA was associated with greater FN-BMD loss than the lowest intake of AA, at the lowest intake of EPA+DHA (P = 0.04), but the highest intake of AA appeared protective against bone loss at higher intakes of EPA+DHA. The strongest protective effects of high intakes of EPA+DHA were observed at high intakes of AA (P < 0.01). High intakes (≥ 3 servings/wk) of fish led to maintenance of FN-BMD over 4-years in men (for dark fish+tuna, dark fish, and tuna), and in women (for dark fish only), compared to losses observed with lower intakes (P < 0.05). Greater intakes of LA in women, but not men, were associated with loss of 4-year change in FN-BMD (P-trend < 0.01).;We then examined associations among dietary essential fatty acids and fish intakes with hip fracture risk in a combined sample of men and women over 17-y follow- up (n=904). Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men, and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Subjects in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs Q1: HR = 0.46, 95% CI = 0.26 to 0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs Q1: HR = 0.20, 95% CI = 0.04 to 0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, fish, LA, or n-6:n-3 ratio.;Finally, we examined associations among plasma phosphatidylcholine (PC) essential fatty acids with cross-sectional FN-BMD (n=771); 4-y change in FN-BMD (n=562); and hip fracture risk (n=771) over 17-y follow-up. PC LA levels were detrimentally associated with FN-BMD in women (P-trend = 0.02). Women and men with the highest PC LA levels had over twice the hip fracture risk than those with the lowest levels (HR = 2.16, 95% CI = 1.09 to 4.26). A protective association was observed between PC AA levels and FN-BMD in men (P-trend = 0.06). Women and men with the highest PC AA levels had a 52% lower hip fracture risk than those with the lowest levels (HR = 0.48, 95% CI = 0.24 to 0.97). PC DHA was detrimentally associated with loss of FN-BMD over 4-y in women (P-trend = 0.04), but was protective in men (P = 0.01).;In conclusion, AA and EPA+DHA may be protective to bone health, but this protection appears dependent on high intakes of both classes of essential fatty acids. ALA may reduce the risk of hip fracture, while LA may be detrimental to bone health.