α-Linolenic acid prevents experimental osteoporosis by inhibiting Ca2+/CaMKIV/p-CREB pathway and typical RANK signaling

Epidemiological studies suggest an association between edible oil intake and the development of osteoporosis. However, whether such a relationship is causal remains to be validated. In this study, we discovered that the administration of diverse edible oils elicited distinct pathological responses within an ovariectomy (OVX)-induced osteoporosis model. Data showed that linseed oil exhibited a great improvement, significantly enhancing biochemical indices related to bone metabolism, biomechanical properties, and microstructure of bone tissue. Notably, diets with different oils altered the fatty acids composition in femur, thus remodeling the homeostasis of bone metabolism. The α-linolenic acid (ALA) content in femur of mice in linseed oil group was increased by 14.71 ± 0.34-fold, representing the most pronounced change among all the groups. Mechanistically, ALA inhibited the proliferation and formation of osteoclast, as well as osteoclastogenesis-related gene expression in vitro. Furthermore, ALA mitigated receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone loss by suppressing the Ca²⁺/CaMKIV/p-CREB pathway and typical RANK signaling. Overall, these findings imply that dietary supplementation with linseed oil could be an effective strategy for OVX-induced osteoporosis, with ALA being the bioactive component conferring the anti-osteoporotic properties of linseed oil.