Evidence presented over the past 20 years has shown that long-chain polyunsaturated fatty acids (LCPUFAs),
especially the n-3 fatty acids such as eicospentaenoic acid (EPA) and docosahexaenoic acid (DHA)
are beneficial for bone health. Some studies in humans indicate that LCPUFAs can increase bone formation,
affect peak bone mass in adolescents and reduce bone loss as measured using bone mineral densitometry.
The cellular mechanisms of action of the LCPUFAs, however, are complex and involve
modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signalling
pathways, cytokines and growth factors. LCPUFAs affect receptor activator of nuclear factor jb (RANK), a
receptor found on the osteoclast, the cell causing bone resorption, which controls osteoclast formation.
Lipoxygenase (LOX) generated lipid mediators (resolvins, lipoxins, protectins and docosanoids) have both
anti-inflammatory and pro-resolving activities. Both resolvins and lipoxins inhibit inflammation-induced
bone resorption. Arachidonic acid significantly upregulates inducible NO synthase (iNOS) mRNA expression
in human osteoblast-like cells, thereby possibly enhancing osteoclastic activity. The protective effect
of EPA on osteoblastogenesis could be mediated by the biphasic cross-talk between PGE2 and NO production
involving COX-2 and iNOS pathways. Other mediators of osteoblast maturation include PPARa
ligands such as linoleic acid and possibly DHA in association with bone morphogenic proteins. Since
DHA is a weaker ligand for PPARc, more uncommitted mesenchymal stem cells are thought to differentiate
into osteoblasts rather than adipocytes. This review addresses selected cellular mechanisms that
may explain the beneficial effects of the LCPUFAs on bone.