The comparative effects of Antarctic krill oil and arachidonic acid-rich oil on bone resorption in ovariectomized mice

Osteoporosis is a global chronic disease affecting over 200 million people worldwide, presenting a substantial medical and socioeconomic burden on modern societies. However, long-term intake of diets supplemented with different polyunsaturated fatty acids (PUFAs) can affect bone metabolism; thus, this study investigated the comparative effects of Antarctic krill oil (AKO, containing n-3 PUFAs) and arachidonic acid-rich oil (AAO, containing n-6 PUFAs) on bone resorption in a postmenopausal osteoporosis model. The mice were orally administrated with AKO (200 mg/kg) or AAO (220 mg/kg) once daily for 30 days, then ovariectomized and followed by the continued administration of respective samples for 90 days. Biomechanical and histomorphometric analysis revealed that AKO increased bone mineral density (BMD) to enhance biomechanical properties by increasing the mineral apposition rate and repairing the microstructure of the trabecular bone, whereas AAO had the opposite effect. Fatty acid analysis of the vertebra showed that AKO increased n-3 PUFAs (especially for DHA) content, thereby decreasing the ratio of n-6/n-3 PUFAs, which was negatively correlated with BMD. However, AAO had the opposite effect due to high amounts of arachidonic acid. To explore the underlying mechanism responsible for these observations, the classical bone resorption OPG/RANKL/NF-κB pathway mediated by PGE2/EP4 and key factors of osteoclastogenesis were compared. The ratio of n-6/n-3 PUFAs in bone affected the production of PGE2, a factor regulating the OPG/RANKL pathway, thereby stimulating the NF-κB pathway to regulate osteoclastogenesis. ELISA, qRT-PCR, and western blot results demonstrated that AKO reduced the key factors of osteoclastogenesis expression via the OPG/RANKL/NF-κB pathway mediated by PGE2/EP4. Arachidonic acid is a precursor of PGE2 synthesis. AAO showed the opposite trend through the RANKL/NF-κB pathway mediated by PGE2/EP4. In conclusion, AKO could significantly improve osteoporosis via the OPG/RANKL/NF-κB pathway mediated by PGE2/EP4 to inhibit osteoclastogenesis, whereas AAO aggravated osteoporosis via the RANKL/NF-κB pathway mediated by PGE2/EP4. This is the first study to systematically compare the effects and mechanism of AKO and AAO in regulating bone resorption in osteoporotic mice to support recommendations on fatty acid types in dietary oils for osteoporosis population.