Saturated fatty acids enhance osteoclast survival.

Hyperlipidemia and marrow fat are associated with lowering bone density in vivo, suggesting that lipid contributes to bone loss. Using bone marrow-derived macrophages, we investigated the effect of saturated fatty acids (SFA) on osteoclastogenesis. The level of free fatty acids and adiposity in bone marrow was significantly elevated in obese mice. SFA increased osteoclast (OC) survival by preventing apoptosis. SFA caused the production of MIP-1alpha and led to activation of nuclear factor (NF)-kappaB in the OC. The absence of Toll-like receptor 4 (TLR4) or myeloid differentiation factor 88 (MyD88) abolished the survival effect of SFA on OC.