Osteoporosis and atherosclerosis are very common diseases associated with elder patients, it has higher incidence rate and more complications, they are the major risk factor for increased mortality. With the increasing of the patient’s age, the clinical connections between them have become increasingly closer. In recent years, OPG/RANKL/RANK pathway is the research high lights and it is a milestone in the research history of osteoporosis. The researchers come to realize that this signal pathway also played an invaluable role in atherosclerosis, enabling researchers conduct extensive research potential between the system and atherosclerosis. This article is about OPG/RANKL/RANK pathway as a bridge connection between them, exploring their common pathogenesis and clinical relationships, for providing further integrated concept in clinical work with these molecules as targets for designing and generating new drugs.