SOST and osteoporosis: This study introduces a SOST-targeted vaccine specifically designed for osteoporosis, demonstrating several advantages: (1) high specificity for the loop 3 domain of SOST, which may confer protective effects against osteoporosis while minimizing cardiovascular side effects; and (2) robust immunogenicity coupled with favorable physicochemical properties, effectively inducing endogenous ROMO-like antibodies.