BACKGROUND: Osteoprotegerin(OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of NF-B ligand(RANKL). OPG has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. Recently, OPG has been proposed as a link molecule between osteoporosis and arterial calcification. However, the relationship between circulating OPG levels and cardiovascular disease in human populations is unclear. Thus, the aim of this study was to investigate the relationship between circulating OPG levels and cardiovascular risk factors in women. METHODS: The subjects were 286 women, with a mean age of 51.5 yr. The blood pressure, body mass index(BMI) and waist to hip ratio(WHR) were examined and the serum concentrations of OPG determined by ELISA. The fasting glucose levels, serum lipid profiles and follicle stimulating hormone (FSH) were measured by standard methods. RESULTS: A significant association was observed between the serum OPG levels, age and WHR(r=0.134, P<0.05). Also, the serum OPG levels were significantly correlated with the serum total cholesterol and low density lipoprotein cholesterol levels(r=0.175, P<0.01; r=0.176, P<0.01). Conversely, there was a nonsignificant relationship between the serum OPG levels, blood pressure and fasting glucose levels. The mean serum OPG levels were found to be about 11% greater in post-than premenopausal women(mean+/-SD, 1358.5+/-380.0 vs. 1228.8+/-407.7pg/mL, respectively(P<0.001). There was a significant association between the serum OPG and serum FSH levels(r=0.176, P<0.01). CONCLUSION: In conclusion, our data show that the levels of circulating OPG are partially associated with the cardiovascular risk factors and female hormonal status in healthy women. These data suggest that OPG may be an important paracrine factor of cardiovascular disease in human female populations.