Table 1.

Associations of polyunsaturated fatty acids with measures of bone health in humans.

Author, Year	Design	Population, N	Fatty Acid(s)	Outcome	Association2
Bone Mineral Density
Rousseau, 2009 [24]	Cross-sectional, pool of 3 studies	Men & Women >60y N=247	Total n-3 Total n-6 Ratio n-6:3	Total Femur	+ Null Null
Jarvinen, 2011 [25]	Cross-sectional, Kuopio OSTPRE Fracture Prevention Study	Women Post-menopausal Without HRT N=221	Total PUFA Total n-3 Linolenic EPA+DHA Total n-6 LA, AA	Lumbar Spine	+ + + Null + Null
Farina, 2011 [26]	Cross-sectional, FOP Study	Men & Women Mean age 75y N=854	ALA, EPA, DHA LA, AA n6:n3 ratio	Femoral Neck	Null Null Null
Farina, 2012 [27]	Cross-sectional, FOP Study	Men Mean age 75y N=484	Plasma: DHA LA AA	Femoral Neck	Null Null -
Virtanen, 2010 [28]	Cross-sectional, Cardiovascular Health Study	Men & Women Mean age 73y N=1,305	Fish EPA + DHA	Femoral Neck	Null Null
Farina, 2011 [26]	Longitudinal, FOP Study	Men Mean age 75y N=623	ALA EPA, DHA EPA+DHA LA AA n6:n3 ratio	Femoral Neck 4y change	Maintenance Lost less (+) Lost less (+) Maintenance Lost less (+) Maintenance
Farina, 2012 [27]	Longitudinal, FOP Study	Men Mean age 75y N=363	Plasma: DHA LA AA	Femoral Neck, 4y change	Lost less (+) Null Null
Lappe, 2013 [32]	Randomized Controlled Trial 6mo	Post-menopausal women N=58	Intervention: 1g PUFA (DHA&EPA)* Control: corn oil & beeswax	Lumbar Spine Femoral Neck Wards triangle Trochanter Total Hip Whole Body	Null Maintenance + Null Null Null
Risk of Fracture
Fan, 2013 [38]	Matched Case-Control	Men & Women Mean age 71y 581 cases	Selected fish intake	Risk of Hip Fracture	Risk (+)
Farina, 2012 [27]	Longitudinal (17y FU), FOP Study	Men & Women Mean age 75y N=765	Plasma: DHA LA AA	Risk of Hip Fracture	Null Null Risk (+)
Farina, 2011 [35]	Longitudinal (11y FU), FOP Study	Men & Women Mean age 75y N=904	ALA EPA, DHA EPA + DHA Linoleic acid AA n6:n3 ratio Fish	Risk of Hip Fracture	Risk (+) Null Null Null Risk (+)** Null Null
Virtanen, 2010 [28]	Longitudinal, (11y FU) Cardiovascular Health Study	Men and Women Mean age 73y N=5,045	Tuna + other fish EPA + DHA	Risk of Hip Fracture	Null Null
Virtanen, 2012 [37]	Longitudinal, (24y FU) Pooled from: NHS Study & Health Professional Follow up Study	Men & Women Mean age 63y N=122,354	Total PUFA Total n-3 ALA, EPA+DHA Total n-6 LA Fish	Risk of Hip Fracture	Null Null Null Null Null Null
Orchard, 2010 [36]	Longitudinal, (7.8y FU) Woman’s Health Initiative	Post-menopausal women N=137,486	PUFA Total n-3 ALA, EPA+DHA Total n-6	Risk of Hip Fracture	Null Null Null Null
Markers of Bone Turnover
Salari, 2010 [34]	Randomized Controlled Trial 6mo	Post-menopausal women N=25	900mg n-3 vs. Placebo	OC, BAP Urine Pyd	Null Null (+)
Martin-Bautista, 2010 [33]	Randomized Controlled Trial 12mo	Hyperlipidemic adults N=72	Fortified milk (0.2g EPA + 0.14g DHA + 5.17g oleic acid), 250ml 2x/d vs.Placebo milk	OPG RANKL OPG/RANKL PTH, CTX OC	(+) (+) (+) Null (+)
Lappe, 2013 [32]	Randomized Controlled Trial 6mo	Post-menopausal women N=58	1g PUFA (DHA&EPA) 3 vs. Placebo	BAP NTx OC, DPD, OPG, RANKL	(+) (+) Null Null

¹Abbreviations used: FOP Study, Framingham Osteoporosis Study; PUFA, polyunsaturated fatty acids; n-3 FA, omega 3 fatty acids; n-6 FA, omega 6 fatty acids; LA, linoleic acid; ALA, alpha-linolenic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; AA, arachidonic acid; FU, follow-up; OC, osteocalcin; BAP, bone-specific alkaline phosphatase; urine Pyd, urinary pyridinoline; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor kappa-B ligand; PTH, parathyroid hormone; CTX, serum collagen type 1 cross-linked C-telopeptide; NTx, urinary N-telopeptide; DPD, urinary free deoxypyridinoline; NHS, Nurses Health Study

²+ denotes a positive relation with bone; - denotes a negative association with bone health.

^*Intervention also included 30mg genistein + 800IU vitamin D3 + 150μg vitamin K1; EPA:DHA ratio of 2:1.

^**Results observed in men only