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To mitigate such pathological bone loss, various therapeutic targets have been identified. Oxidative stress is one of the main contributing factors in the promotion of osteoclastogenesis. Herein, using a template\u2010assisted approach, hollow ruthenium oxide (RuO<jats:sub>2<\/jats:sub>) nanospheres are synthesized as an effective antioxidant for the treatment of CoCrMo alloy particles\u2010induced osteolysis. Hollow RuO<jats:sub>2<\/jats:sub> significantly suppressed receptor activator of nuclear factor kappa\u2010B ligand (RANKL)\u2010induced osteoclastogenesis, bone resorption, and the expression of specific markers (including NFATc1, c\u2010Fos, MMP9, CTSK, and DC\u2010STAMP) of bone marrow\u2010derived macrophages via inhibition of the nuclear factor kappa\u2010B (NF\u2010\u03baB) and tumor necrosis factor (TNF)\u2010\u03b1 pathways. In mouse calvaria, hollow RuO<jats:sub>2<\/jats:sub> nanozymes demonstrate an appreciable attenuation in osteoclast differentiation, bone loss, and soft tissue malformations induced by CoCrMo alloy particles. 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