Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study

Am J Clin Nutr. 2015 May;101(5):947-55. doi: 10.3945/ajcn.114.087502. Epub 2015 Mar 18.


Background: Polyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake.

Objective: We aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk.

Design: Osteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression.

Results: In men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98).

Conclusions: Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex.

Keywords: aging; bone health; fatty acids; fish oil; omega-3; osteoporotic fracture.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arachidonic Acid / blood
  • Eicosapentaenoic Acid / blood
  • Fatty Acids, Omega-3 / blood*
  • Fatty Acids, Omega-6 / blood*
  • Female
  • Fish Oils / administration & dosage*
  • Follow-Up Studies
  • Humans
  • Male
  • Osteoporotic Fractures / blood*
  • Osteoporotic Fractures / prevention & control
  • Phospholipids / blood*
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Surveys and Questionnaires


  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fish Oils
  • Phospholipids
  • Arachidonic Acid
  • Eicosapentaenoic Acid