This study, for the first time, links AKR1A1 lactylation—a candidate immunometabolic marker—to the SPP1–CD44-mediated bone marrow immune communication network, proposing the “AKR1A1–SPP1–CD44” axis as a novel signaling pathway involved in osteoporosis pathogenesis. The gene discussed is AKR1A1; the disease is osteoporosis.