Protaetia brevitarsis seulensis Larvae Extract Attenuates Inflammatory Osteoclast Differentiation and Bone Loss

<b>Background/Objectives:</b> The larvae of <i>Protaetia brevitarsis seulensis</i> (PB), an edible insect, exhibit diverse bioactivities, but their effects on inflammatory bone loss remain unclear. We investigated whether a 70% ethanol extract of PB larvae (PBE) suppresses osteoclast differentiation and bone loss under inflammatory conditions. <b>Methods:</b> Osteoclast differentiation was assessed in co-cultures of mouse bone marrow cells and osteocytic cells stimulated with interleukin-1 (IL-1). Direct effects on osteoclast precursors were tested in bone marrow-derived macrophages exposed to receptor activator of nuclear factor-κB ligand (RANKL) or tumor necrosis factor-α (TNF-α). Skeletal effects were evaluated in a mouse model of lipopolysaccharide (LPS)-induced bone loss. <b>Results:</b> PBE inhibited IL-1-induced osteoclast differentiation in co-culture, reduced osteocytic RANKL expression and prostaglandin E2 (PGE2) production, and dampened early IL-1 signaling. In osteoclast precursors, PBE directly suppressed osteoclastogenesis driven by RANKL or TNF-α. In vivo, PBE attenuated LPS-induced bone loss and blunted the associated increases in bone RANKL and PGE2. <b>Conclusions:</b> PBE limits inflammatory osteoclastogenesis by downregulating PGE2 and RANKL production in osteoclast-supporting cells and directly inhibiting osteoclast precursor differentiation, thereby attenuating LPS-induced bone loss. These findings identify PBE as a food-derived candidate for managing inflammation-associated bone loss and support further preclinical and nutritional intervention studies.